Publications by authors named "Henrik Hjalgrim"

217 Publications

Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes.

J Transl Genet Genom 2021 17;5:200-217. Epub 2021 Jun 17.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Aim: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk.

Methods: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis.

Results: We discovered positive associations between FROH and CLL (β = 21.1, SE = 4.41, = 1.6 × 10) and FL (β = 11.4, SE = 5.82, = 0.02) but not DLBCL ( = 1.0) or MZL ( = 0.91). For F3, we observed an association with CLL (β = 27.5, SE = 6.51, = 2.4 × 10). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity.

Conclusion: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk.
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http://dx.doi.org/10.20517/jtgg.2021.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494431PMC
June 2021

Impact of COVID-19 Pandemic on Sleep Quality, Stress Level and Health-Related Quality of Life-A Large Prospective Cohort Study on Adult Danes.

Int J Environ Res Public Health 2021 07 17;18(14). Epub 2021 Jul 17.

Department of Clinical Immunology, Zealand University Hospital, 4600 Køge, Denmark.

The everyday lives of Danish inhabitants have been affected by the COVID-19 pandemic, e.g., by social distancing, which was employed by the government in March 2020 to prevent the spread of SARS-CoV-2. Moreover, the pandemic has entailed economic consequences for many people. This study aims to assess changes in physical and mental health-related quality of life (MCS, PCS), in stress levels, and quality of sleep during the COVID-19 pandemic and to identify factors that impact such changes, using a prospective national cohort study including 26,453 participants from the Danish Blood Donor Study who answered a health questionnaire before the pandemic and during the pandemic. Descriptive statistics, multivariable linear and multinomial logistic regression analyses were applied. A worsening of MCS and quality of sleep was found, and an overall decrease in stress levels was observed. PCS was decreased in men and slightly increased in women. The extent of health changes was mainly affected by changes in job situation, type of job, previous use of anti-depressive medication and the participants' level of personal stamina. Thus, living under the unusual circumstances that persisted during the COVID-19 pandemic has had a negative impact on the health of the general population. This may, in time, constitute a public health problem.
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http://dx.doi.org/10.3390/ijerph18147610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307688PMC
July 2021

Hyperhidrosis and the risk of being treated for skin infections.

J Dermatolog Treat 2021 Jul 5:1-7. Epub 2021 Jul 5.

Department of Dermatology, Zealand University Hospital, University of Copenhagen, Roskilde, Denmark.

Background: A few studies have described an increased prevalence of skin infections in individuals with hyperhidrosis compared to others. However, it remains uncertain whether hyperhidrosis is an independent risk factor for skin infections.

Objective: To compare the risk of skin infections in individuals with and without hyperhidrosis.

Methods: In this retrospective cohort study, data on hyperhidrosis were collected from the Danish Blood Donor Study. Blood donors included in 2010-2019 were followed from inclusion until December 2019. Data on redeemed prescriptions against skin infections were collected from the National Prescription Register. The intensity of prescription-use by hyperhidrosis status was assessed in Andersen-Gill models.

Results: Overall, 4,176 (9.6%) of 43,477 blood donors had self-reported hyperhidrosis and 437 (0.34%) of 127,823 blood donors had hospital diagnosed hyperhidrosis. Self-reported hyperhidrosis was associated with the use of antibiotic prescriptions (adjusted hazard ratio = 1.21; 95% confidence interval 1.00-1.45,  = 0.047). Hospital diagnosed hyperhidrosis was associated with the use of antibiotic (adjusted hazard ratio = 1.33; 95% confidence interval 1.03-1.68,  = 0.028) and topical antifungal prescriptions (adjusted hazard ratio = 1.43; 95% confidence interval 1.04-1.97,  = 0.027).

Conclusions: Hyperhidrosis is associated with the use of prescriptions for antibiotics and topical antifungals. This suggests a clinically relevant association between hyperhidrosis and skin infections.
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http://dx.doi.org/10.1080/09546634.2021.1944971DOI Listing
July 2021

Combinations of self-reported rhinitis, conjunctivitis, and asthma predicts IgE sensitization in more than 25,000 Danes.

Clin Transl Allergy 2021 Mar;11(1):e12013

Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.

Background: Allergic rhinitis (AR), allergic conjunctivitis (AC), and asthma composing multiple phenotypes and improved understanding of these phenotypes and their respective risk factors are needed.

Objectives: The objective of this study was to define the prevalence of AR, AC, and asthma and their association with allergen-specific immunoglobulin E (sIgE) sensitization in a large cohort of blood donors and identify risk factors.

Methods: From the nationwide population-based Danish Blood Donor Study, 52,976 participants completed an electronic questionnaire including AR, AC, asthma, allergic predisposition, and childhood residence. Of these, 25,257 were additionally tested for sIgE to inhalation allergens (Phadiatop).

Results: The prevalence of sIgE sensitization, AR, AC, and asthma was 30%, 19%, 15%, and 9%, respectively. The youngest birth cohorts had the highest prevalence of sIgE sensitization and symptoms of asthma, AR, and AC, and for asthma, they apparently experienced symptoms at an earlier age. The sIgE sensitization was positively associated with male sex. The sIgE seroprevalence was higher in participants with both AR and AC (ARC) than in participants with either AR or AC. Allergic predisposition and sIgE sensitization increased the risk of the diseases, while farm upbringing was associated with reduced prevalence of ARC, however, only in sIgE sensitized participants.

Conclusion: Birth year, childhood residence, sIgE sensitization, and allergic predisposition were associated with asthma, AR, and AC prevalence. Individuals with self-reported ARC represent a primarily sIgE-positive phenotype, while those with either AR or AC represent more diverse phenotypes.
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http://dx.doi.org/10.1002/clt2.12013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099331PMC
March 2021

Epidemiology of Hyperhidrosis in Danish Blood Donors.

Acta Derm Venereol 2021 Apr 26;101(4):adv00435. Epub 2021 Apr 26.

Department of Dermatology, Zealand University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, DK-4000 Roskilde, Denmark. E-mail:

The risk factors and disease implications of hyper-hidrosis are unknown. The objectives of this retrospective cohort study were to estimate the prevalence of hyperhidrosis and to compare demographic, life-style, and socioeconomic parameters in blood donors with and without self-reported or hospital-diagnosed hyperhidrosis. The study included blood donors from the Danish Blood Donor Study for the period 2010-2019. Registry data were collected from Statistics Denmark. Overall, 2,794 of 30,808 blood donors (9.07%; 95% confidence interval (95% CI) 8.75-9.40) had self- reported hyperhidrosis and 284 of 122,225 (0.23%; 95% CI 0.21-0.26) had hospital-diagnosed hyperhidrosis. Self-reported hyperhidrosis was associated with smoking (odds ratio (OR) 1.17; 95% CI 1.05-1.31), overweight (OR 1.72; 95% CI 1.58-1.87), "unemployed" (OR 1.60; 95% CI 1.24-2.08), "short education" (OR 0.76; 95% CI 0.64-0.90), and lower income (beta-coefficient -26,121; 95% CI -37,931, -14,311). Hospital-diagnosed hyperhidrosis did not differ from controls. Thus, self-reported hyperhidrosis was associated with potential hyperhidrosis risk factors (smoking, overweight) and disease implications (unemployment, low education level and income).
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http://dx.doi.org/10.2340/00015555-3790DOI Listing
April 2021

Revisiting IL-6 expression in the tumor microenvironment of classical Hodgkin lymphoma.

Blood Adv 2021 03;5(6):1671-1681

Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, and.

Interleukin-6 (IL-6) can induce therapeutic resistance for several cancer agents currently used to treat classical Hodgkin lymphoma (cHL). We aimed to investigate whether the presence of IL-6+ leukocytes and IL-6+ Hodgkin-Reed-Sternberg (HRS) cells in the tumor microenvironment (TME) was associated with adverse survival outcomes, expression of other immune markers, and serum IL-6 levels. We used a contemporarily treated cohort (n = 136), with a median follow-up of 13.8 years (range, 0.59-15.9 years). We performed immunohistochemistry with an IL-6 antibody on tissue microarrays from diagnostic biopsies of cHL patients. Patients with IL-6+ leukocytes ≥1% (n = 54 of 136) had inferior event-free survival (hazard ratio [HR] = 3.58; 95% confidence interval [CI], 1.80-7.15) and overall survival (HR = 6.71; 95% CI, 2.51-17.99). The adverse survival was maintained in multivariate Cox regression and propensity score-matched analyses, adjusting for well-known poor-prognostic covariates. The presence of IL-6+ HRS cells and high serum IL-6 levels were not associated with survival. IL-6+ leukocytes correlated with increased proportions of IL-6+ HRS cells (P < .01), CD138+ plasma cells (P < .01), CD68+ macrophages (P = .02), and tryptase-positive mast cells (P < .01). IL-6+ HRS cells correlated with increased proportions of CD68+ macrophages (P = .03), programmed death-ligand 1-positive (PD-L1+) leukocytes (P = .04), and PD-L1+ HRS cells (P < .01). Serum-IL-6 lacked correlation with IL-6 expression in the TME. This is the first study highlighting the adverse prognostic impact of IL-6+ leukocytes in the TME in a cohort of contemporarily treated adult patients with cHL.
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http://dx.doi.org/10.1182/bloodadvances.2020003664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993098PMC
March 2021

Genetically Raised Circulating Bilirubin Levels and Risk of Ten Cancers: A Mendelian Randomization Study.

Cells 2021 02 15;10(2). Epub 2021 Feb 15.

Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), 69008 Lyon, France.

Bilirubin, an endogenous antioxidant, may play a protective role in cancer development. We applied two-sample Mendelian randomization to investigate whether genetically raised bilirubin levels are causally associated with the risk of ten cancers (pancreas, kidney, endometrium, ovary, breast, prostate, lung, Hodgkin's lymphoma, melanoma, and neuroblastoma). The number of cases and their matched controls of European descent ranged from 122,977 and 105,974 for breast cancer to 1200 and 6417 for Hodgkin's lymphoma, respectively. A total of 115 single-nucleotide polymorphisms (SNPs) associated ( < 5 × 10) with circulating total bilirubin, extracted from a genome-wide association study in the UK Biobank, were used as instrumental variables. One SNP (rs6431625) in the promoter region of the uridine-diphosphoglucuronate glucuronosyltransferase1A1 ( gene explained 16.9% and the remaining 114 SNPs (non- SNPs) explained 3.1% of phenotypic variance in circulating bilirubin levels. A one-standarddeviation increment in circulating bilirubin (≈ 4.4 µmol/L), predicted by non- SNPs, was inversely associated with risk of squamous cell lung cancer and Hodgkin's lymphoma (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.73-0.99, 0.04 and OR 0.64, 95% CI 0.42-0.99, 0.04, respectively), which was confirmed after removing potential pleiotropic SNPs. In contrast, a positive association was observed with the risk of breast cancer after removing potential pleiotropic SNPs (OR 1.12, 95% CI 1.04-1.20, 0.002). There was little evidence for robust associations with the other seven cancers investigated. Genetically raised bilirubin levels were inversely associated with risk of squamous cell lung cancer as well as Hodgkin's lymphoma and positively associated with risk of breast cancer. Further studies are required to investigate the utility of bilirubin as a low-cost clinical marker to improve risk prediction for certain cancers.
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http://dx.doi.org/10.3390/cells10020394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918902PMC
February 2021

The impact of health-related quality of life and depressive symptoms on blood donor career-Results from the Danish blood donor study.

Transfusion 2021 05 2;61(5):1479-1488. Epub 2021 Mar 2.

Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: Blood donors report better health-related quality of life (HRQL) than non-donors. Likewise, donors reporting good health are less likely to stop donating and have a higher donation frequency. This is evidence of the healthy donor effect (HDE). This study is the first to investigate the impact of HRQL and depressive symptoms on subsequent donor career.

Study Design And Methods: Prospective cohort study includes 102,065 participants from the Danish Blood Donor Study applying the 12-item short-form health survey (SF-12) measuring a mental (MCS) and a physical component score (PCS) and the Major Depression Inventory (MDI). Poisson and Cox regression models were used to assess the effect of SF-12 and MDI scores on donation frequency and donor cessation. Higher MCS/PCS scores indicate good HRQL, while higher MDI score indicates higher experience of depressive symptoms.

Results: For both sexes, MCS was positively correlated with donation frequency for up to 5 years, and similarly for PCS among women. A negative correlation between MDI score and donation frequency in the year following assessment was observed only among men. No correlation was observed among women. An increase in both MCS and PCS was associated with a lower risk of donation cessation in both sexes, while an increase in MDI score was only associated with an increased risk of donation cessation in men.

Conclusion: MCS, PCS, and MDI score affect donor career. Thus, adjusting for donation frequency may reduce HDE-bias in donor health research. However, because of the small effect sizes, other ways of quantifying HDE may be beneficial.
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http://dx.doi.org/10.1111/trf.16336DOI Listing
May 2021

Mapping comorbidity in chronic lymphocytic leukemia: impact of individual comorbidities on treatment, mortality, and causes of death.

Leukemia 2021 09 18;35(9):2570-2580. Epub 2021 Feb 18.

Department of Hematology, Odense University Hospital, Odense, Denmark.

Comorbid conditions are highly prevalent in chronic lymphocytic leukemia (CLL), nevertheless, detailed information on the association of specific comorbidities with CLL prognosis is missing. Using Danish, nation-wide registers, we followed consecutive patients from CLL-diagnosis in 1997-2018, until death or end of follow-up. Sub-grouping of comorbidities was defined using a modified Charlson comorbidity index. Patients were matched on sex, date of birth (±1 month), and region of residency with up to ten comparators from the general population. In total, 9170 patients with CLL were included in the study, with a median of 5.0 years of follow-up. All comorbid conditions studied were individually associated with increased mortality, and many also with increased cause-specific mortality, related or unrelated to CLL. Comorbidity correlated with increased mortality from infections and cardiovascular disease. CLL patients, particularly older, had a significant loss of lifetime compared with the general population. This study highlights a large subgroup of comorbid CLL patients with an unmet treatment-need and missing efficacy and safety data on treatment, who are under-prioritized in clinical trials. Also, studies assessing interventions that may provide better tolerability of treatment in older or comorbid patients, with cancer in general, and CLL in particular, are warranted.
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http://dx.doi.org/10.1038/s41375-021-01156-xDOI Listing
September 2021

Twenty-five years of triptans - a nationwide population study.

Cephalalgia 2021 07 14;41(8):894-904. Epub 2021 Feb 14.

Department of Neurology, Danish Headache Center, Copenhagen University Hospital, Glostrup, Denmark.

Background: The efficacy of triptans as the main acute treatment strategy for migraine headache at the population-wide level needs to be understood to inform clinical decision-making. We summarise key trends in triptan use using more than 25 years of Danish nationwide data.

Methods: We conducted a nationwide register-based cohort study based on all Danish residents with access to public healthcare between 1 January 1994 and 31 October 2019 and summarise informative trends of all purchases of triptans in Denmark in the same period. Complete purchase records of Sumatriptan, Naratriptan, Zolmitriptan, Rizatriptan, Almotriptan, Eletriptan, and Frovatriptan were used.

Findings: Over a 25-year period, triptan use increased from 345 to 945 defined daily doses (DDD) per 1000 inhabitants per year and the yearly prevalence of triptan use increased from 5.17 to 14.57 per 1000 inhabitants. Between 2014 and 2019, 12.3% of the Danish migraine population purchased a triptan. Following their initial purchase, 43% of patients had not repurchased triptans within 5 years. At most, 10% of patients indicating triptan discontinuation tried more than one triptan. The prevalence of triptan overuse, defined as having purchased at least 20 DDDs of triptans per month for 3 consecutive months, increased in parallel with the prevalence of triptan use, prevalent in 56 of every 1000 triptan users every year between 2014 and 2019.

Interpretation: In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance.
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http://dx.doi.org/10.1177/0333102421991809DOI Listing
July 2021

Risk of new malignancies among patients with CLL treated with chemotherapy: results of a Danish population-based study.

Br J Haematol 2021 04 11;193(2):339-345. Epub 2021 Feb 11.

Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Patients with chronic lymphocytic leukaemia (CLL) have an increased risk of new malignancies. However, limited data have been published about the impact of CLL treatment on this risk. Here we followed a Danish population-based cohort of CLL patients for risks of new malignancies. Patients in the Danish CLL registry (2008-2017) were included. Up to 50 CLL-free matched comparators were identified. First-line treatment was categorized into four groups; bendamustine, chlorambucil, fludarabine or other. Patients were followed from CLL diagnosis for individual types of malignancy. Adjusted hazard ratios (HR) for new malignancies and 95% confidence intervals (95% CI) were calculated. Overall, 4286 CLL patients and 214 150 controls developed 594 and 20 565 new malignancies respectively. Risk of new malignancies was increased for CLL patients. Chemotherapy treatment was registered for 1064 (25%) patients with CLL. Chemotherapy was associated with increased HR (1·51, 95% CI: 1·3-1·8) of any new malignancy. Specifically, fludarabine was associated with an increased risk of myelodysplastic syndrome (MDS) (HR 4·93, 95% CI: 1·2-19·8). Patients with CLL are at increased risk of other haematological and solid malignancies compared to the general population. Chemotherapy exposure is associated with increased risk of second malignancies and fludarabine is associated with increased risk of MDS.
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http://dx.doi.org/10.1111/bjh.17337DOI Listing
April 2021

A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.

Commun Biol 2021 02 3;4(1):156. Epub 2021 Feb 3.

deCODE genetics/Amgen Inc., Reykjavik, Iceland.

Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation.
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http://dx.doi.org/10.1038/s42003-020-01575-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859200PMC
February 2021

Estimation of SARS-CoV-2 Infection Fatality Rate by Real-time Antibody Screening of Blood Donors.

Clin Infect Dis 2021 01;72(2):249-253

Department of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark.

Background: The pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has tremendous consequences for our societies. Knowledge of the seroprevalence of SARS-CoV-2 is needed to accurately monitor the spread of the epidemic and to calculate the infection fatality rate (IFR). These measures may help the authorities make informed decisions and adjust the current societal interventions. The objective was to perform nationwide real-time seroprevalence surveying among blood donors as a tool to estimate previous SARS-CoV-2 infections and the population-based IFR.

Methods: Danish blood donors aged 17-69 years giving blood 6 April to 3 May were tested for SARS-CoV-2 immunoglobulin M and G antibodies using a commercial lateral flow test. Antibody status was compared between geographical areas, and an estimate of the IFR was calculated. Seroprevalence was adjusted for assay sensitivity and specificity taking the uncertainties of the test validation into account when reporting the 95% confidence intervals (CIs).

Results: The first 20 640 blood donors were tested, and a combined adjusted seroprevalence of 1.9% (95% CI, .8-2.3) was calculated. The seroprevalence differed across areas. Using available data on fatalities and population numbers, a combined IFR in patients <70 years is estimated at 89 per 100 000 (95% CI, 72-211) infections.

Conclusions: The IFR was estimated to be slightly lower than previously reported from other countries not using seroprevalence data. The IFR is likely severalfold lower than the current estimate. We have initiated real-time nationwide anti-SARS-CoV-2 seroprevalence surveying of blood donations as a tool in monitoring the epidemic.
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http://dx.doi.org/10.1093/cid/ciaa849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337681PMC
January 2021

Maternal diabetes and risk of multiple sclerosis in the offspring: A Danish nationwide register-based cohort study.

Mult Scler 2021 10 17;27(11):1686-1694. Epub 2020 Dec 17.

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

Background: Previous studies suggest a 3- to-10-fold increased risk of multiple sclerosis (MS) in offspring of mothers with diabetes mellitus (DM).

Objectives: To examine MS risk in offspring of diabetic mothers, overall and according to type of maternal DM, that is, pregestational DM or gestational DM, as well as to examine MS risk among offspring of diabetic fathers.

Methods: The study cohort included all 1,633,436 singletons born in Denmark between 1978 and 2008. MS diagnoses were identified in the Danish Multiple Sclerosis Registry, and parental DM diagnoses in the National Patient Register. We used Cox proportional hazards regression analyses to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of parental DM with MS risk in the offspring.

Results: MS risk among individuals whose mothers had pregestational DM was 2.3-fold increased compared with that among individuals with nondiabetic mothers (HR = 2.25; 95% CI: 1.35-3.75,  = 15). MS risk was statistically non-significant among offspring of mothers with gestational DM (HR = 1.03 (95% CI: 0.49-2.16),  = 7) and among offspring of diabetic fathers (HR = 1.40 (95% CI: 0.78-2.54),  = 11).

Conclusion: Our nationwide cohort study utilizing high-quality register data in Denmark over several decades corroborates the view that offspring of diabetic mothers may be at an elevated risk of developing MS.
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http://dx.doi.org/10.1177/1352458520977120DOI Listing
October 2021

SARS-CoV-2 infection fatality rate among elderly retired Danish blood donors - A cross-sectional study.

Clin Infect Dis 2020 Oct 26. Epub 2020 Oct 26.

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

Background: Despite the vast majority of individuals succumbing to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are elderly, infection fatality rate (IFR) estimates for the age group 70 years older are still scarce. To this end we assessed SARS-CoV-2 seroprevalence among retired blood donors and combined it with national COVID-19 survey data to provide reliable population-based IFR estimates for this age group.

Methods: We identified 60,926 retired blood donors age 70 years or older in the rosters of three region-wide Danish blood banks and invited them to fill in a questionnaire on COVID-19 related symptoms and behaviours. Among 24,861 (40.8%) responders, we invited a random sample of 3,200 individuals for blood testing. Overall, 1,201 (37.5%) individuals were tested for SARS-CoV-2 antibodies (Wantai) and compared to 1,110 active blood donors age 17-69 years. Seroprevalence 95% confidence intervals (CI) were adjusted for assay sensitivity and specificity.

Results: Among retired (age 70 years or older) and active (age 17-69 years) blood donors, adjusted seroprevalences were 1.4% (95% CI: 0.3%-2.5%) and 2.5% (95% CI: 1.3%-3.8%), respectively. Using available population data on COVID-19 related fatalities, IFRs for patients age 70 years or older and for 17-69 years were estimated at 5.4% (95% CI: 2.7%-6.4%) and 0.083% (95% CI: 0.054%-0.18%), respectively. Only 52.4% of SARS-CoV-2 seropositive retired blood donors reported having been sick since the start of the pandemic.

Conclusion: COVID-19 IFR in the age group above 69 years is estimated to be 65 times as high as the IFR for people age 18-69 years.
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http://dx.doi.org/10.1093/cid/ciaa1627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665387PMC
October 2020

The Swedish Scandinavian donations and transfusions database (SCANDAT3-S) - 50 years of donor and recipient follow-up.

Transfusion 2020 12 21;60(12):3019-3027. Epub 2020 Aug 21.

Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.

Background: The two previous versions of the Scandinavian donations and transfusions (SCANDAT) databases, encompassing data on blood donors, blood components, transfusions, and transfused patients linked to national health registers in Sweden and Denmark up until 2012, have been used to study donor health, disease transmission, the role of donor characteristics, and more.

Study Design And Methods: Here we describe the creation of the Swedish portion of the third iteration of SCANDAT - SCANDAT3-S - with follow-up from 1968 to the end of 2017, resulting in up to 50 years of uninterrupted follow-up for donors and recipients. The database now also includes non-transfused non-donors with a blood typing result, increased temporal resolution for transfusions, and linkages to laboratory and drug prescription data.

Results: After data cleaning, the database contained 23 579 863 donation records, 21 383 317 transfusion records, and 8 071 066 unique persons with valid identification. In total, the database offers 28 638 436 person-years of follow-up for donors, 13 582 350 person-years of follow-up for transfusion recipients, and 65 613 639 person-years of follow-up for non-recipient non-donors, with possibility for future extension. Additionally, the database includes 167 820 412 dispense records for prescribed drugs and 316,338,442 laboratory test results. Since the latest update in 2012, >99.9% of all donations were traceable to a donor with valid identification, and >97% of all transfusions to a recipient with valid identification.

Conclusion: With extended follow-up and more clinical detail, the Swedish portion of the third and latest iteration of the SCANDAT database should allow for more comprehensive analysis of donation and transfusion-related research questions.
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http://dx.doi.org/10.1111/trf.16027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754339PMC
December 2020

Danish premature birth rates during the COVID-19 lockdown.

Arch Dis Child Fetal Neonatal Ed 2021 Jan 11;106(1):93-95. Epub 2020 Aug 11.

Department of Neonatology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

To explore the impact of COVID-19 lockdown on premature birth rates in Denmark, a nationwide register-based prevalence proportion study was conducted on all 31 180 live singleton infants born in Denmark between 12 March and 14 April during 2015-2020.The distribution of gestational ages (GAs) was significantly different (p=0.004) during the lockdown period compared with the previous 5 years and was driven by a significantly lower rate of extremely premature children during the lockdown compared with the corresponding mean rate for the same dates in the previous years (OR 0.09, 95% CI 0.01 to 0.40, p<0.001). No significant difference between the lockdown and previous years was found for other GA categories.The reasons for this decrease are unclear. However, the lockdown has provided a unique opportunity to examine possible factors related to prematurity. Identification of possible causal mechanisms might stimulate changes in clinical practice.
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http://dx.doi.org/10.1136/archdischild-2020-319990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7421710PMC
January 2021

Antimicrobial use before chronic lymphocytic leukemia: a retrospective cohort study.

Leukemia 2021 03 20;35(3):747-751. Epub 2020 Jul 20.

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

Chronic lymphocytic leukemia (CLL) is accompanied by increased risk of potentially fatal infections. While this can mostly be attributed to disease-related immune dysfunction, it is not known if CLL patients are also constitutionally susceptible to infections. We linked nation-wide Danish registers to explore this possibility, approximating infection susceptibility by use of antimicrobials. We assessed the incidence of antimicrobials among CLL patients and matched controls from the general population for up to 22 years before index diagnosis, and among children and grandchildren of CLL patients and their matched controls. Our analyses showed that for CLL patients overall antimicrobial use began to increase gradually six years before leukemia diagnosis. Before this time point, CLL patients had used significantly more macrolides (relative risk = 1.15; 95% confidence interval 1.10-1.20), antimycotics (1.18; 1.08-1.30), and antivirals (1.62; 1.45-1.81) than controls for up to 22 years before diagnosis. The same pattern of increased use was found among CLL patients' children and grandchildren. Our study suggests that CLL diagnosis is preceded by decades of increased susceptibility to infections. The duration of this time window is compatible with causal roles of immune dysfunction and/or certain infections in CLL pathogenesis, possibly mediating the association between constitutional infection susceptibility and CLL risk.
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http://dx.doi.org/10.1038/s41375-020-0980-0DOI Listing
March 2021

The value of circulating microRNAs for early diagnosis of B-cell lymphoma: A case-control study on historical samples.

Sci Rep 2020 06 15;10(1):9637. Epub 2020 Jun 15.

Department of Clinical Immunology, Naestved Hospital, Naestved, Denmark.

MicroRNAs are small regulatory RNAs that are deregulated in a wide variety of human cancers, including different types of B-cell lymphoma. Nevertheless, the feasibility of circulating microRNA for early diagnosis of B-cell lymphoma has not been established. To address the possibility of detecting specific circulating microRNAs years before a B-cell lymphoma is diagnosed, we studied the plasma expression of microRNA first in pre-treatment samples from patients with diffuse large B-cell lymphoma and subsequently in repository samples from blood donors who later developed B-cell lymphomas. In addition, we studied the microRNA expression in the diagnostic lymphoma biopsy. The most strongly induced (miR-326) and suppressed (miR-375) plasma microRNA at diagnosis, when compared with healthy blood donors, were also substantially up- or down-regulated in plasma repository samples taken from several months to up to two years before the blood donors were diagnosed with B-cell lymphoma. Importantly, at these time points the donors had no signs of disease and felt healthy enough to donate blood. In conclusion, this first study of plasma microRNA profiles from apparently healthy individuals, taken several years before B-cell lymphoma diagnosis, suggests that plasma microRNA profiles may be predictive of lymphoma development.
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http://dx.doi.org/10.1038/s41598-020-66062-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295742PMC
June 2020

Differences and Temporal Changes in Risk of Invasive Pneumococcal Disease in Adults with Hematological Malignancies: Results from a Nationwide 16-Year Cohort Study.

Clin Infect Dis 2021 02;72(3):463-471

Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.

Background: Patients with hematological malignancies (HM) are known to carry an increased risk of invasive pneumococcal disease (IPD). However, temporal variations in IPD risks following a cancer diagnosis remain poorly characterized. To inform vaccine guidelines and patient management, we assessed the IPD incidence among patients with HM and other malignancies.

Methods: The study population included all individuals aged ≥15 years during 2000-2016 in Denmark. Variations in incidences of IPD over time and between different types of hematological malignancies and diagnoses were assessed by Poisson regression.

Results: During 85 002 224 person-years of observation, 13 332 episodes of a first IPD were observed, of which 765 (5.7%) occurred among individuals with HM. Among HM patients, the IPD incidence rate decreased continuously during the study period (rate ratio per year, 0.91; 95% confidence interval, .90-.92). The risk of IPD in patients with HM was up to 39 times higher when compared to the background population and was highest for multiple myeloma, acute lymphoblastic leukemia, and chronic lymphocytic leukemia. Unlike other malignancies, the increased IPD risk did not wane with the time since HM diagnosis. We found a vaccination uptake of only ≤2% in patients with HM and ≤1% for those with other types of malignancies.

Conclusions: Adults with HM in general and patients with lymphoid malignancies in particular have an increased risk for IPD, compared with patients with other types of cancer and with individuals free of cancer. The pneumococcal vaccination uptake is extremely low in this at risk-population. Efforts to prevent IPD in HM patients are continuously warranted.
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http://dx.doi.org/10.1093/cid/ciaa090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850540PMC
February 2021

Correction to: Infectious mononucleosis, immune genotypes, and non-Hodgkin lymphoma (NHL): an InterLymph Consortium study.

Cancer Causes Control 2020 06;31(6):607

Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Unfortunately, the word "Group" is missed in the article title of the original publication. It has been corrected by this erratum.
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http://dx.doi.org/10.1007/s10552-020-01297-xDOI Listing
June 2020

No evidence of transfusion transmitted sporadic Creutzfeldt-Jakob disease: results from a bi-national cohort study.

Transfusion 2020 04 18;60(4):694-697. Epub 2020 Mar 18.

Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.

Background: Creutzfeldt-Jakob disease (CJD) is an uncommon, invariably fatal, neurodegenerative disorder that presents as progressive dementia with concurrent motor symptoms and myoclonia. The pathophysiology involves prion protein misfolding and spreading in a self-catalyzed manner. It has been shown to be transmissible through tissue transplants. Variant CJD (vCJD), a subtype of the disease is also transmissible through transfusion of blood products. This study aims to corroborate the scarce data that suggest that sporadic CJD (sCJD) is not transmitted via blood transfusion.

Methods And Study Design: A retrospective cohort study was performed, using data from the bi-national Scandinavian Donations and Transfusions (SCANDAT2) database containing data on blood donors, donations, transfusions, and transfused patients in Sweden and Denmark since 1968 and 1982, respectively. Mortality and medical data were collected from nationwide health care and population registries. Donors with subsequent CJD were identified, as well as recipients of blood products from these donors. A second analysis was performed, screening for clustering of CJD cases from donors without a CJD diagnosis.

Results: We identified 39 donors with a subsequent diagnosis of sCJD. No cases of CJD occurred among the 883 recipients of blood products from these donors. A total of 89 CJD cases were identified among recipients of transfusions. No clustering of cases from the same donor occurred.

Discussion: Using data from a large, bi-national database of transfused patients, we find no evidence of sCJD transmission. Our data adds to the growing body of evidence indicating that sCJD is not transfusion transmitted.
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http://dx.doi.org/10.1111/trf.15751DOI Listing
April 2020

The donors perceived positive and negative effects of blood donation.

Transfusion 2020 03;60(3):553-560

Department of Clinical Immunology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.

Background: Occasionally blood donation has a negative influence on some donors, while others express feelings of increased energy or wellbeing after donation. Some donors even report symptoms such as headache or feelings of unease indicating "it is time to donate blood again." This study aims to determine symptoms and frequencies of blood donors experiencing positive and negative effects of blood donation, and study possible associations with sex, age, body mass index, smoking status, and hemoglobin level.

Study Design And Methods: We developed and validated a questionnaire with eight predefined physical and psychological symptoms related to blood donation using a 5-point Likert Scale. Participants in The Danish Blood Donor Study were asked to indicate if they experienced the present symptom prior to and/or after the donation.

Results: A total of 6,073 donors were included. Of the donors, 61% experienced one or more effects of blood donation. Positive effects were experienced by 18% of the donors, 29% experienced negative effects, and 14% experienced both. Most notable positive effects were alleviated headache (14%), feeling lighter (14%), and less tiredness (7%). Most notable negative effects were less energy (25%), more dizziness (22%), and more tiredness (21%). Logistic regression analysis revealed that positive effects were more likely among donors with higher BMI, older donors, and smokers. Negative effects were more likely among younger donors, donors with lower BMI, and among female donors.

Conclusion: Analyses indicate that susceptibility to blood donation effects varies by BMI, sex, smoking status, and age, and therefore should be taken into consideration when informing donors about potential effects of blood donation.
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http://dx.doi.org/10.1111/trf.15717DOI Listing
March 2020

Infectious mononucleosis, immune genotypes, and non-Hodgkin lymphoma (NHL): an InterLymph Consortium study.

Cancer Causes Control 2020 05 2;31(5):451-462. Epub 2020 Mar 2.

Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Purpose: We explored the interaction between non-Hodgkin lymphoma (NHL), infectious mononucleosis (IM) history, and immune-related genotypes in a pooled case-control analysis.

Methods: A total of 7,926 NHL patients and 10,018 controls from 12 case-control studies were included. Studies were conducted during various time periods between 1988 and 2008, and participants were 17-96 years of age at the time of ascertainment/recruitment. Self-reported IM history and immune response genotypes were provided by the InterLymph Data Coordinating Center at Mayo Clinic. Odds ratios (OR) were estimated using multivariate logistic regression, and interactions were estimated using the empirical Bayes method. P was used to account for multiple comparisons.

Results: There was evidence of an interaction effect between IM history and two variants on T-cell lymphoma (TCL) risk: rs1143627 in interleukin-1B (IL1B) (p = 0.04, OR = 0.09, 95% confidence interval [CI] 0.01, 0.87) and rs1800797 in interleukin-6 (IL6) (p = 0.03, OR = 0.08, 95% CI 0.01, 0.80). Neither interaction effect withstood adjustment for multiple comparisons. There were no statistically significant interactions between immune response genotypes and IM on other NHL subtypes.

Conclusions: Genetic risk variants in IL1B and IL6 may affect the association between IM and TCL, possibly by influencing T-cell activation, growth, and differentiation in the presence of IM, thereby decreasing risk of immune cell proliferation.
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http://dx.doi.org/10.1007/s10552-020-01266-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534692PMC
May 2020

Lipid Trait Variants and the Risk of Non-Hodgkin Lymphoma Subtypes: A Mendelian Randomization Study.

Cancer Epidemiol Biomarkers Prev 2020 05 27;29(5):1074-1078. Epub 2020 Feb 27.

Emory University, Atlanta, Georgia.

Background: Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis.

Methods: Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated ( < 5 × 10) with high-density lipoprotein (HDL, = 164), low-density lipoprotein (LDL, = 137), total cholesterol (TC, = 161), and triglycerides (TG, = 123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8%, and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance-weighted method, estimating odds ratios (OR) per standard deviation and 95% confidence intervals (CI).

Results: HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00-1.30) and MZL (OR = 1.09; 95% CI, 1.01-1.18), while TG was inversely associated with MZL risk (OR = 0.90; 95% CI, 0.83-0.99), all at nominal significance ( < 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99-1.19; = 0.087). No associations were noteworthy after adjusting for multiple testing.

Conclusions: We did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes.

Impact: Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196490PMC
May 2020

Genetically Determined Height and Risk of Non-hodgkin Lymphoma.

Front Oncol 2019 28;9:1539. Epub 2020 Jan 28.

Interdisciplinary Department of Medicine, University of Bari, Bari, Italy.

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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http://dx.doi.org/10.3389/fonc.2019.01539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999122PMC
January 2020

Nationwide prediction of type 2 diabetes comorbidities.

Sci Rep 2020 02 4;10(1):1776. Epub 2020 Feb 4.

The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Identification of individuals at risk of developing disease comorbidities represents an important task in tackling the growing personal and societal burdens associated with chronic diseases. We employed machine learning techniques to investigate to what extent data from longitudinal, nationwide Danish health registers can be used to predict individuals at high risk of developing type 2 diabetes (T2D) comorbidities. Leveraging logistic regression-, random forest- and gradient boosting models and register data spanning hospitalizations, drug prescriptions and contacts with primary care contractors from >200,000 individuals newly diagnosed with T2D, we predicted five-year risk of heart failure (HF), myocardial infarction (MI), stroke (ST), cardiovascular disease (CVD) and chronic kidney disease (CKD). For HF, MI, CVD, and CKD, register-based models outperformed a reference model leveraging canonical individual characteristics by achieving area under the receiver operating characteristic curve improvements of 0.06, 0.03, 0.04, and 0.07, respectively. The top 1,000 patients predicted to be at highest risk exhibited observed incidence ratios exceeding 4.99, 3.52, 1.97 and 4.71 respectively. In summary, prediction of T2D comorbidities utilizing Danish registers led to consistent albeit modest performance improvements over reference models, suggesting that register data could be leveraged to systematically identify individuals at risk of developing disease comorbidities.
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http://dx.doi.org/10.1038/s41598-020-58601-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000818PMC
February 2020

Cytokine Autoantibodies Are Associated with Infection Risk and Self-Perceived Health: Results from the Danish Blood Donor Study.

J Clin Immunol 2020 02 15;40(2):367-377. Epub 2020 Jan 15.

Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark.

The presence of naturally occurring cytokine-specific autoantibodies (c-aAb) in humans is well established, as well as associations to selected pathologies. However, the overall influence of c-aAb on immunocompetence remains largely unknown. In this paper, we performed a large-scale investigation of c-aAb association with infection risk. A cohort of healthy Danish blood donors was screened for c-aAb against IL-1α, IL-6, IL-10, IFNα, and GM-CSF using a Luminex-based multiplex assay, and results were linked to data from the Danish National Prescription Registry. The filing of an antimicrobial prescription following c-aAb measurement was used as a proxy for impaired immunocompetence. We found that c-aAb against pro-inflammatory cytokines IFNα and GM-CSF tended to associate with increased risk of prescription filings in women, whereas antibodies against anti-inflammatory IL-10 were associated with a lower predicted risk of antimicrobial prescriptions, as well as higher self-perceived health scores. We also observed an association of cumulative c-aAb presence with prescription risk. Our data show that cytokine autoantibodies in healthy individuals associate with various proxies for immunomodulation, with the exact association dependent on the pattern of pro- or anti-inflammatory cytokines targeted. This suggests that c-aAb may express cytokine-modulatory properties in healthy individuals and may be critical to further investigate as biomarkers of immunodeficiency.
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http://dx.doi.org/10.1007/s10875-020-00744-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082412PMC
February 2020

Hemoglobin concentration and risk of arterial and venous thrombosis in 1.5 million Swedish and Danish blood donors.

Thromb Res 2020 02 20;186:86-92. Epub 2019 Dec 20.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Södersjukhuset, Stockholm, Sweden.

Introduction: There are conflicting results whether elevated hematocrit is associated with an increased risk of thromboembolic events in individuals without polycythemia vera. To assess the risk of vascular events in relation to hemoglobin concentration, we conducted a large population-based cohort study based on Scandinavian health registers.

Materials And Methods: We included 1,538,019 Swedish and Danish blood donors between 1987 and 2012. Hazard ratios (HRs) of arterial and venous thrombosis were estimated using Cox regression. Additionally, we fitted person-stratified models where each donor was compared only to him-/herself.

Results: The risk of myocardial infarction and ischemic stroke increased with higher hemoglobin concentration in both men and women. The HRs for myocardial infarction and ischemic stroke in men with hemoglobin concentration ≥ 17.5 g/dL were 3.52 (95% confidence interval [CI], 2.85-4.36) and 2.36 (95% CI, 1.63-3.43), respectively, compared to the reference group. The corresponding HRs for women with hemoglobin concentration ≥ 16.0 g/dL were 3.22 (2.12-4.89) and 2.35 (1.37-4.02) for myocardial infarction and ischemic stroke, respectively. The risk of venous thrombosis was highest in men with subnormal hemoglobin concentration (<13.0 g/dL), HR 1.69 (95% CI, 1.40-2.04). In the person-stratified model, the association between elevated hemoglobin concentration and risk of myocardial infarction was attenuated but remained significant.

Conclusions: In this large cohort of Scandinavian blood donors, elevated hemoglobin concentration was associated with an increased risk of vascular events, primarily arterial events. Even though associations were weakened when each person served as their own control, a high hemoglobin concentration may serve as a cardiovascular risk marker.
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http://dx.doi.org/10.1016/j.thromres.2019.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654700PMC
February 2020

Migraine polygenic risk score associates with efficacy of migraine-specific drugs.

Neurol Genet 2019 Dec 24;5(6):e364. Epub 2019 Oct 24.

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.

Objective: To assess whether the polygenic risk score (PRS) for migraine is associated with acute and/or prophylactic migraine treatment response.

Methods: We interviewed 2,219 unrelated patients at the Danish Headache Center using a semistructured interview to diagnose migraine and assess acute and prophylactic drug response. All patients were genotyped. A PRS was calculated with the linkage disequilibrium pred algorithm using summary statistics from the most recent migraine genome-wide association study comprising ∼375,000 cases and controls. The PRS was scaled to a unit corresponding to a twofold increase in migraine risk, using 929 unrelated Danish controls as reference. The association of the PRS with treatment response was assessed by logistic regression, and the predictive power of the model by area under the curve using a case-control design with treatment response as outcome.

Results: A twofold increase in migraine risk associates with positive response to migraine-specific acute treatment (odds ratio [OR] = 1.25 [95% confidence interval (CI) = 1.05-1.49]). The association between migraine risk and migraine-specific acute treatment was replicated in an independent cohort consisting of 5,616 triptan users with prescription history (OR = 3.20 [95% CI = 1.26-8.14]). No association was found for acute treatment with non-migraine-specific weak analgesics and prophylactic treatment response.

Conclusions: The migraine PRS can significantly identify subgroups of patients with a higher-than-average likelihood of a positive response to triptans, which provides a first step toward genetics-based precision medicine in migraine.
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http://dx.doi.org/10.1212/NXG.0000000000000364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878840PMC
December 2019
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