Publications by authors named "Rebecca D Jackson"

187 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

Sports with a Bat or Racket are Not Associated with Thumb-base Osteoarthritis.

J Athl Train 2021 Aug 17. Epub 2021 Aug 17.

Timothy E. McAlindon, MD, MPH, Chief, Division of Rheumatology, Allergy, & Immunology, Tufts Medical Center, Boston, MA, USA,

Context: Repetitive joint use is a risk factor for osteoarthritis, which is a leading cause of disability. Sports requiring a bat or racket to perform repetitive high-velocity impacts may increase the risk of thumb-base osteoarthritis. However, this hypothesis remains untested.

Objective: To determine if a history of participation in racket or bat sports is associated with the prevalence of thumb-base osteoarthritis.

Design: Descriptive epidemiology study.

Setting: Osteoarthritis Initiative. Four clinical sites in the United States.

Participants: We included men and women from the recruited from the community. Eligible participants had dominant hand radiographic readings, hand symptom assessments, and historical physical activity survey data.

Main Outcome Measures: A history of exposure to racket or bat sports (baseball/softball, racquetball/squash, badminton, table tennis, tennis [doubles/singles]) was based on self-reported recall data covering 3 age ranges (12-18 years, 19-34 years, 35-49 years). Prevalent radiographic thumb-base osteoarthritis was defined as someone with Kellgren-Lawrence grade≥2 in the first carpometacarpal joint or scaphotrapezoidal joint at the OAI baseline visit. Symptomatic thumb-base osteoarthritis was defined as the presence of radiographic osteoarthritis and hand/finger symptoms.

Results: In total, we included 2309 participants. Among 1049 men, 355 (34%) and 56 (5%) had radiographic or symptomatic thumb-base osteoarthritis, respectively; and among 1260 women, 535 (42%) and 170 (13%), respectively. After adjusting for age, race, and education level, we found no statistically significant associations between a history of any racket or bat sport participation and thumb-base osteoarthritis (radiographic or symptomatic; odds ratios range from 0.82 to 1.34).

Conclusions: Within a community-based cohort, a self-reported history of participation in racket or bat sports was not associated with an increased odds of having radiographic or symptomatic thumb-base osteoarthritis in the dominant hand.
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http://dx.doi.org/10.4085/1062-6050-0208.21DOI Listing
August 2021

Genetic insights into biological mechanisms governing human ovarian ageing.

Nature 2021 08 4;596(7872):393-397. Epub 2021 Aug 4.

Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.

Reproductive longevity is essential for fertility and influences healthy ageing in women, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
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http://dx.doi.org/10.1038/s41586-021-03779-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611832PMC
August 2021

Response to "Letter to the Editor on 'Altered gait mechanics are associated with severity of chondropathy after hip arthroscopy for femoroacetabular impingement' by Brown-Taylor L, Wilson J, McNally M, et al. (Gait Posture 2020; 77: 175-181)".

Gait Posture 2021 07 15;88:238-239. Epub 2021 May 15.

Division of Physical Therapy, School of Health and Rehabilitation Sciences, The Ohio State University, 453 W 10th Avenue, Suite 516, Columbus, OH, 43210, United States; Sports Medicine Research Institute, The Ohio State University Wexner Medical Center, 2835 Fred Taylor Drive, Suite 3200, Columbus, OH, 43202, United States. Electronic address:

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http://dx.doi.org/10.1016/j.gaitpost.2021.05.015DOI Listing
July 2021

Immediate impact of the COVID-19 pandemic on CTSA TL1 and KL2 training and career development.

J Clin Transl Sci 2020 Jun 29;4(6):556-561. Epub 2020 Jun 29.

Center for Leading Innovation and Collaboration, Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, USA.

Clinical and Translational Science Award (CTSA) TL1 trainees and KL2 scholars were surveyed to determine the immediate impact of the COVID-19 pandemic on training and career development. The most negative impact was lack of access to research facilities, clinics, and human subjects, plus for KL2 scholars lack of access to team members and need for homeschooling. TL1 trainees reported having more time to think and write. Common strategies to maintain research productivity involved time management, virtual connections with colleagues, and shifting to research activities not requiring laboratory/clinic settings. Strategies for mitigating the impact of the COVID-19 pandemic on training and career development are described.
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http://dx.doi.org/10.1017/cts.2020.504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605410PMC
June 2020

A System for Phenotype Harmonization in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Program.

Am J Epidemiol 2021 10;190(10):1977-1992

Genotype-phenotype association studies often combine phenotype data from multiple studies to increase statistical power. Harmonization of the data usually requires substantial effort due to heterogeneity in phenotype definitions, study design, data collection procedures, and data-set organization. Here we describe a centralized system for phenotype harmonization that includes input from phenotype domain and study experts, quality control, documentation, reproducible results, and data-sharing mechanisms. This system was developed for the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program, which is generating genomic and other -omics data for more than 80 studies with extensive phenotype data. To date, 63 phenotypes have been harmonized across thousands of participants (recruited in 1948-2012) from up to 17 studies per phenotype. Here we discuss challenges in this undertaking and how they were addressed. The harmonized phenotype data and associated documentation have been submitted to National Institutes of Health data repositories for controlled access by the scientific community. We also provide materials to facilitate future harmonization efforts by the community, which include 1) the software code used to generate the 63 harmonized phenotypes, enabling others to reproduce, modify, or extend these harmonizations to additional studies, and 2) the results of labeling thousands of phenotype variables with controlled vocabulary terms.
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http://dx.doi.org/10.1093/aje/kwab115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485147PMC
October 2021

Urinary Phthalate Biomarkers and Bone Mineral Density in Postmenopausal Women.

J Clin Endocrinol Metab 2021 06;106(7):e2567-e2579

Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.

Context: Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone.

Objective: We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women's Health Initiative (WHI).

Methods: We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N = 1255). We measured 13 phthalate biomarkers and creatinine in 2 to 3 urine samples per participant collected over 3 years, when all participants were cancer free. Total hip and femoral neck BMD were measured at baseline and year 3, concurrent with urine collection, via dual-energy x-ray absorptiometry. We fit multivariable generalized estimating equation models and linear mixed-effects models to estimate cross-sectional and longitudinal associations, respectively, with stratification on postmenopausal hormone therapy (HT) use.

Results: In cross-sectional analyses, mono-3-carboxypropyl phthalate and the sum of di-isobutyl phthalate metabolites were inversely associated with total hip BMD among HT nonusers, but not among HT users. Longitudinal analyses showed greater declines in total hip BMD among HT nonusers and with highest concentrations of mono-3-carboxyoctyl phthalate (-1.80%; 95% CI, -2.81% to -0.78%) or monocarboxynonyl phthalate (-1.84%; 95% CI, -2.80% to -0.89%); similar associations were observed with femoral neck BMD. Among HT users, phthalate biomarkers were not associated with total hip or femoral neck BMD change.

Conclusion: Certain phthalate biomarkers are associated with greater percentage decreases in total hip and femoral neck BMD. These findings suggest that phthalate exposure may have clinically important effects on BMD, and potentially fracture risk.
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http://dx.doi.org/10.1210/clinem/dgab189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266434PMC
June 2021

Topical Corticosteroids and Glucocorticoid-Induced Osteoporosis-Cumulative Dose and Duration Matter.

JAMA Dermatol 2021 03;157(3):269-270

Center for Clinical and Translational Science, The Ohio State University, Columbus.

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http://dx.doi.org/10.1001/jamadermatol.2020.4967DOI Listing
March 2021

Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease.

Nat Commun 2020 12 18;11(1):6417. Epub 2020 Dec 18.

The Institute for Translational Genomics and Population Sciences, Department of Pediatrics and Los Angeles Biomedical Research Institute, Harbor-UCLA, Torrance, CA, USA.

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529:p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10) without being associated with liver enzymes or non-fasting blood glucose. Silencing of ZNF529 in human hepatoma cells results in upregulation of LDL receptor and increased LDL uptake in the cells. This suggests that inhibition of ZNF529 or its gene product should be prioritized as a novel candidate drug target for treating dyslipidemia and associated CVD.
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http://dx.doi.org/10.1038/s41467-020-20086-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749177PMC
December 2020

A Meta-Analysis of the Transferability of Bone Mineral Density Genetic Loci Associations From European to African Ancestry Populations.

J Bone Miner Res 2021 03 18;36(3):469-479. Epub 2020 Dec 18.

Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.

Genetic studies of bone mineral density (BMD) largely have been conducted in European populations. We therefore conducted a meta-analysis of six independent African ancestry cohorts to determine whether previously reported BMD loci identified in European populations were transferable to African ancestry populations. We included nearly 5000 individuals with both genetic data and assessments of BMD. Genotype imputation was conducted using the 1000G reference panel. We assessed single-nucleotide polymorphism (SNP) associations with femoral neck and lumbar spine BMD in each cohort separately, then combined results in fixed effects (or random effects if study heterogeneity was high, I index >60) inverse variance weighted meta-analyses. In secondary analyses, we conducted locus-based analyses of rare variants using SKAT-O. Mean age ranged from 12 to 68 years. One cohort included only men and another cohort included only women; the proportion of women in the other four cohorts ranged from 52% to 63%. Of 56 BMD loci tested, one locus, 6q25 (C6orf97, p = 8.87 × 10 ), was associated with lumbar spine BMD and two loci, 7q21 (SLC25A13, p = 2.84 × 10 ) and 7q31 (WNT16, p = 2.96 × 10 ), were associated with femoral neck BMD. Effects were in the same direction as previously reported in European ancestry studies and met a Bonferroni-adjusted p value threshold, the criteria for transferability to African ancestry populations. We also found associations that met locus-specific Bonferroni-adjusted p value thresholds in 11q13 (LRP5, p < 2.23 × 10 ), 11q14 (DCDC5, p < 5.35 × 10 ), and 17p13 (SMG6, p < 6.78 × 10 ) that were not tagged by European ancestry index SNPs. Rare single-nucleotide variants in AKAP11 (p = 2.32 × 10 ), MBL2 (p = 4.09 × 10 ), MEPE (p = 3.15 × 10 ), SLC25A13 (p = 3.03 × 10 ), STARD3NL (p = 3.35 × 10 ), and TNFRSF11A (p = 3.18 × 10 ) were also associated with BMD. The majority of known BMD loci were not transferable. Larger genetic studies of BMD in African ancestry populations will be needed to overcome limitations in statistical power and to identify both other loci that are transferable across populations and novel population-specific variants. © 2020 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353846PMC
March 2021

Introduction to the special issue on the HEALing Communities Study.

Drug Alcohol Depend 2020 12 1;217:108327. Epub 2020 Oct 1.

Center on Drug and Alcohol Research, Department of Behavioral Science, Pharmacology and Psychiatry, College of Medicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, United States.

The severity of the overdose epidemic underscores the urgent need for innovative and high impact interventions that promote the rapid penetration and scale up of evidence-based practices (EBPs) in communities profoundly affected by fatal opioid overdose. This special issue shares scientific advancements in implementation research design and evaluation of a novel data-driven community-based intervention. The HEALing (Helping End Addiction Long-Term) Communities Study (HCS) is a four-year study that is designed to examine the effectiveness of the Communities That HEAL (CTH) intervention. The CTH intervention supports the dissemination of EBPs in 67 communities across four high-burdened states-Kentucky, Massachusetts, New York, and Ohio. The diversity in these communities in terms of rural-urban status, race-ethnicity and other social determinants of health facilitates generalizability of results to other communities across the US. The nine papers in this special issue describe critical elements that constitute the HCS framework and design. This includes the implementation of EBPs that have a substantial impact on fatal and non-fatal opioid overdose, the Opioid-overdose Reduction Continuum of Care Approach, communication campaigns to increase awareness and demand for EBPs and reduce stigma against people with OUD and MOUD interventions, and the process of community engagement. This includes how to form community coalitions and gain their commitment, and steps taken to mobilize coalitions to pursue EBP implementation and ensure EBPs are adapted for community needs. The collective papers in this issue demonstrate that the design of any complex study must adapt to unanticipated temporal events, including the rapidly emerging COVID-19 crisis. Readers will learn about the scientific process of the design and implementation of a community-engaged intervention, its methodologies, guiding conceptual models, and research implementation strategies that can be applied to address other health issues.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528891PMC
December 2020

Serial Bone Density Measurement and Incident Fracture Risk Discrimination in Postmenopausal Women.

JAMA Intern Med 2020 09;180(9):1232-1240

Division of Epidemiology & Community Health, Department of Medicine, University of Minnesota and Veterans Affairs Health Care System, Minneapolis.

Importance: Repeated bone mineral density (BMD) testing to screen for osteoporosis requires resources. For patient counseling and optimal resource use, it is important for clinicians to know whether repeated BMD measurement (compared with baseline BMD measurement alone) improves the ability to discriminate between postmenopausal women who will and will not experience a fracture.

Objective: To assess whether a second BMD measurement approximately 3 years after the initial assessment is associated with improved ability to estimate fracture risk beyond the baseline BMD measurement alone.

Design, Setting, And Participants: The Women's Health Initiative is a prospective observational study. Participants in the present cohort study included 7419 women with a mean (SD) follow-up of 12.1 (3.4) years between 1993 and 2010 at 3 US clinical centers. Data analysis was conducted between May 2019 and December 2019.

Main Outcomes And Measures: Incident major osteoporotic fracture (ie, hip, clinical spine, forearm, or shoulder fracture), hip fracture, baseline BMD, and absolute change in BMD were assessed. The area under the receiver operating characteristic curve (AU-ROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD were calculated to assess incident fracture risk discrimination during follow-up.

Results: Of 7419 participants, the mean (SD) age at baseline was 66.1 (7.2) years, the mean (SD) body mass index was 28.7 (6.0), and 1720 (23%) were nonwhite individuals. During the study follow-up (mean [SD] 9.0 [3.5] years after the second BMD measurement), 139 women (1.9%) experienced hip fractures, and 732 women (9.9%) experienced major osteoporotic fracture. In discriminating between women who experience hip fractures and those who do not, AU-ROC values were 0.71 (95% CI, 0.67-0.75) for baseline total hip BMD, 0.61 (95% CI, 0.56-0.65) for change in total hip BMD, and 0.73 (95% CI, 0.69-0.77) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar discrimination for hip fracture. For discrimination of major osteoporotic fracture, AU-ROC values were 0.61 (95% CI, 0.59-0.63) for baseline total hip BMD, 0.53 (95% CI, 0.51-0.55) for change in total hip BMD, and 0.61 (95% CI, 0.59-0.63) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar ability to discriminate between women who experienced major osteoporotic fracture and those who did not. Associations between change in bone density and fracture risk did not differ by subgroup, including diabetes, age, race/ethnicity, body mass index, or baseline BMD T score.

Conclusions And Relevance: The findings of this study suggest that a second BMD assessment approximately 3 years after the initial measurement was not associated with improved discrimination between women who did and did not experience subsequent hip fracture or major osteoporotic fracture beyond the baseline BMD value alone and should not routinely be performed.
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http://dx.doi.org/10.1001/jamainternmed.2020.2986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385675PMC
September 2020

Corrigendum to "Altered gait mechanics are associated with severity of chondropathy after hip arthroscopy for femoroacetabular impingement syndrome" [Gait Posture 77 (2020) 175-181].

Gait Posture 2020 Jul 16. Epub 2020 Jul 16.

Division of Physical Therapy, School of Health and Rehabilitation Sciences, The Ohio State University, 453 W 10th Avenue, Suite 516, Columbus, OH, 43210, United States; Sports Medicine Research Institute, The Ohio State University Wexner Medical Center, 2835 Fred Taylor Drive, Suite 3200, Columbus, OH, 43202, United States.

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http://dx.doi.org/10.1016/j.gaitpost.2020.07.001DOI Listing
July 2020

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.

Nat Commun 2020 05 21;11(1):2542. Epub 2020 May 21.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
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http://dx.doi.org/10.1038/s41467-020-15706-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242331PMC
May 2020

Personalized training pathways for translational science trainees: Building on a framework of knowledge, skills, and abilities across the translational science spectrum.

J Clin Transl Sci 2020 Apr 19;4(2):102-107. Epub 2020 Feb 19.

The Center for Clinical and Translational Science and Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.

Background: In order to conduct translational science, scientists must combine domain-specific expertise with knowledge on how to identify and cross translational hurdles, and insights on positioning discoveries for the next translational stage. Expert educators from the Clinical and Translational Science Awards (CTSA) Consortium identified 97 knowledge, skills, and abilities (KSAs) important to include in training programs for translational scientists. To assist educators and trainees to use these KSAs, a conceptual model called "Personalized Pathways" was developed that prioritizes KSAs based on trainee background, research area, or phenotype, and expertise on the research team.

Purpose: To understand how CTSA educators prioritize specific KSAs when developing personalized training plans for different translational phenotypes and to identify areas of similarity and difference across phenotypes.

Methods: A web-based, cross-sectional survey of CTSA educators was done. For a selected phenotype, respondents recommended one of four levels of mastery for each of the 97 KSAs. Results were tabulated by frequency, weighted by importance, and divided into tertiles representing high, middle, and lower priority KSAs. Agreement across phenotypes was compared using Krippendorff's alpha.

Results: Ten KSAs were high training priority for Preclinical, Clinical, and Community-Engaged phenotypes. These address research methods, responsible conduct of research, team building, and communicating research results. Nine KSAs were in the next tertile for priority reflecting KSAs in biostatistics, bioinformatics, regulatory precepts, and translating implications of research findings.

Conclusion: A smaller set of KSAs can be prioritized for training Preclinical-, Clinical-, and Community-Engaged researchers. Future work should explore this approach for other phenotypes.
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http://dx.doi.org/10.1017/cts.2019.445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159805PMC
April 2020

Cardiovascular Outcomes in Relation to Antihypertensive Medication Use in Women with and Without Cancer: Results from the Women's Health Initiative.

Oncologist 2020 08 6;25(8):712-721. Epub 2020 Apr 6.

Harbor-University of California Los Angeles Medical Center, Los Angeles, California, USA.

Background: Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard clinical endpoints. Within a prospective study, we examined the risk of heart failure (HF) and coronary heart disease (CHD) events in relation to use of commonly used antihypertensive medications, including ACEis/ARBs, BBs, calcium channel blockers (CCB), and diuretics, comparing women with and without cancer.

Materials And Methods: In a cohort of 56,997 Women's Health Initiative study participants free of cardiovascular disease who received antihypertensive treatment, we used multivariable-adjusted Cox regression models to calculate the hazard ratios (HRs) of developing CHD, HF, and a composite outcome of cardiac events (combining CHD and HF) in relation to use of ACEis/ARBs, CCBs, or diuretics versus BBs, separately in women with and without cancer.

Results: Whereas there was no difference in risk of cardiac events comparing ACEi/ARB with BB use among cancer-free women (HR = 0.99 [0.88-1.12]), among cancer survivors ACEi/ARB users were at a 2.24-fold risk of total cardiac events (1.18-4.24); p-interaction = .06). When investigated in relation to CHD only, an increased risk was similarly observed in ACEi/ARB versus BB use for cancer survivors (HR = 1.87 [0.88-3.95]) but not in cancer-free women (HR = 0.91 [0.79-1.06]; p-interaction = .04). A similar pattern was also seen in relation to HF but did not reach statistical significance (p-interaction = .23).

Conclusion: These results from this observational study suggest differing risks of cardiac events in relation to antihypertensive medications depending on history of cancer. Although these results require replication before becoming actionable in a clinical setting, they suggest the need for more rigorous examination of the effect of antihypertensive choice on long-term cardiac outcomes in cancer survivors.

Implications For Practice: Although additional research is needed to replicate these findings, these data from a large, nationally representative sample of postmenopausal women indicate that beta blockers are favorable to angiotensin-converting enzyme inhibitors in reducing the risk of cardiac events among cancer survivors. This differs from the patterns observed in a noncancer cohort, which largely mirrors what is found in the randomized clinical trials in the general population.
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http://dx.doi.org/10.1634/theoncologist.2019-0977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418354PMC
August 2020

Author Correction: Genome-wide association study of knee pain identifies associations with GDF5 and COL27A1 in UK Biobank.

Commun Biol 2020 Mar 26;3(1):149. Epub 2020 Mar 26.

Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s42003-020-0880-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098975PMC
March 2020

Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians.

J Foot Ankle Res 2020 Mar 4;13(1):11. Epub 2020 Mar 4.

University of Maryland School of Medicine, Baltimore, MD, USA.

Background: Hallux valgus, one of the most common structural foot deformities, is highly heritable. However, previous efforts to elucidate the genetic underpinnings of hallux valgus through a genome-wide association study (GWAS) conducted in 4409 Caucasians did not identify genome-wide significant associations with hallux valgus in both gender-specific and sex-combined GWAS meta-analyses. In this analysis, we add newly available data and more densely imputed genotypes to identify novel genetic variants associated with hallux valgus.

Methods: A total of 5925 individuals of European Ancestry were categorized into two groups: 'hallux valgus present' (n = 2314) or 'no deformity' (n = 3611) as determined by trained examiners or using the Manchester grading scale. Genotyping was performed using commercially available arrays followed by imputation to the Haplotype Reference Consortium (HRC) reference panel version 1.1. We conducted both sex-specific and sex-combined association analyses using logistic regression and generalized estimating equations as appropriate in each cohort. Results were then combined in a fixed-effects inverse-variance meta-analyses. Functional Mapping and Annotation web-based platform (FUMA) was used for positional mapping, gene and gene-set analyses.

Results: We identified a novel locus in the intronic region of CLCA2 on chromosome 1, rs55807512 (OR = 0.48, p = 2.96E-09), an expression quantitative trait locus for COL24A1, a member of the collagen gene family.

Conclusion: In this report of the largest GWAS of hallux valgus to date, we identified a novel genome-wide significant locus for hallux valgus. Additional replication and functional follow-up will be needed to determine the functional role of this locus in hallux valgus biology.
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http://dx.doi.org/10.1186/s13047-020-0379-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057609PMC
March 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

Altered gait mechanics are associated with severity of chondropathy after hip arthroscopy for femoroacetabular impingement syndrome.

Gait Posture 2020 03 11;77:175-181. Epub 2019 Nov 11.

Division of Physical Therapy, School of Health and Rehabilitation Sciences, The Ohio State University, 453 W 10th Avenue, Suite 516, Columbus, OH 43210, United States; Sports Medicine Research Institute, The Ohio State University Wexner Medical Center, 2835 Fred Taylor Drive, Suite 3200, Columbus, OH 43202, United States.

Background: Suboptimal patient-reported function and movement impairments often persist after hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Individuals with FAIS with preoperative cartilage pathology (ie. chondropathy) demonstrate distinct movement patterns and have worse post-operative outcomes. It is unknown whether the presence of chondropathy after surgery negatively affects movement and function.

Research Question: Do sagittal plane gait mechanics differ based on chondropathy severity following arthroscopy for FAIS?

Methods: A cross-sectional walking gait analysis was performed for 25 participants post-arthroscopy (2.48 ± 1.38y) and 12 healthy controls (HCs). Peak total support moment (TSM) and relative contributions of the hip, knee, and ankle were calculated during loading response. The Hip Osteoarthritis MRI Scoring System was used to categorize the FAIS group into no-mild or moderate-severe chondropathy groups based on 3 T magnetic resonance imaging of their surgical hip. The interactions of group by limb were evaluated for kinetic variables, covaried by gait speed.

Results: Groups did not differ based on age, BMI and sex distribution (P ≥ 0.14). 13 participants with FAIS presented with moderate-severe chondropathy and 12 presented with no-mild chondropathy. Participants with moderate-severe chondropathy walked significantly slower than both other groups (P = 0.006) and demonstrated lower peak TSM than those with no-mild chondropathy (P = 0.002). Participants with no-mild chondropathy demonstrated lower hip (61.5 %) and greater ankle (17.7 %) contributions to the TSM on the involved limb compared to the moderate-severe group (hip:73.4 %, P = 0.07; ankle:10.5 %, P = 0.007).

Significance: Slower gait speed alone did not explain the lower TSM strategy in participants with moderate-severe chondropathy. Interestingly, the joint contribution strategy of this group was not different than HCs. Participants with no-mild chondropathy demonstrated a TSM strategy that shifted the demand away from their hip and toward their ankle. Given the small sample size, and large variability in joint strategies, future work needs to examine whether these alterations in gait strategy, with or without advanced chondropathy, impact patient function.
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http://dx.doi.org/10.1016/j.gaitpost.2019.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138257PMC
March 2020

History of etidronate.

Bone 2020 05 3;134:115222. Epub 2020 Jan 3.

Procter & Gamble Pharmaceuticals, 8700 Mason Montgomery Road, Mason, OH 45040, USA. Electronic address:

Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva. The first approved clinical use (1977) was for treatment of Paget's disease of bone. Other approved indications are hypercalcemia of malignancy and heterotopic ossification, with a host of off-label uses (including fibrous dysplasia, periodontal disease, multiple myeloma, neuropathic arthropathy, pulmonary microlithiasis, diabetic retinopathy, bone metastases, melorheostosis, urinary stone disease, periodontal disease, etc.). Unique among bisphosphonates, etidronate (oral therapy) results in hyperphosphatemia, increased tubular reabsorption of phosphorus and increased levels of 1,25-dihydroxyvitamin D. The dose that reduces bone resorption is close to the dose that impairs mineralization; prolonged high-dose use can result in osteomalacia and bone fractures. Intermittent cyclic etidronate for osteoporosis resulted in favorable changes in bone density and histomorphometry (no mineralization defect) as well as a decrease in vertebral fracture rates in postmenopausal women with osteoporosis. Later studies showed similar effects in men with osteoporosis and patients with glucocorticoid-induced osteoporosis. Although its use for osteoporosis has given way to newer bisphosphonates and other agents, because of its unique properties, it remains the bisphosphonate of choice for treatment of heterotopic ossification.
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http://dx.doi.org/10.1016/j.bone.2020.115222DOI Listing
May 2020

A phenome-wide association study (PheWAS) in the Population Architecture using Genomics and Epidemiology (PAGE) study reveals potential pleiotropy in African Americans.

PLoS One 2019 31;14(12):e0226771. Epub 2019 Dec 31.

Cleveland Institute for Computational Biology, Cleveland, Ohio, United States of America.

We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African Americans as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study. The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio-metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p<0.01 in two or more PAGE study sites for two or more phenotype classes. We further annotated these PheWAS-identified variants using publicly available functional data and local genetic ancestry. Amongst our novel findings is SPARC rs4958487, associated with increased glucose levels and hypertension. SPARC has been implicated in the pathogenesis of diabetes and is also known to have a potential role in fibrosis, a common consequence of multiple conditions including hypertension. The SPARC example and others highlight the potential that PheWAS approaches have in improving our understanding of complex disease architecture by identifying novel relationships between genetic variants and an array of common human phenotypes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226771PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938343PMC
April 2020

Musculoskeletal Pain, Physical Function, and Quality of Life After Bariatric Surgery.

Pediatrics 2019 12 19;144(6). Epub 2019 Nov 19.

Nationwide Children's Hospital, Columbus, Ohio.

Objectives: To evaluate the longitudinal effects of metabolic and bariatric surgery (MBS) on the prevalence of musculoskeletal and lower extremity (LE) pain, physical function, and health-related quality of life.

Methods: The Teen Longitudinal Assessment of Bariatric Surgery study (NCT00474318) prospectively collected data on 242 adolescents undergoing MBS at 5 centers over a 3-year follow-up. Joint pain and physical function outcomes were assessed by using the Health Assessment Questionnaire Disability Index, Impact of Weight on Quality of Life - Kids, and the Short Form 36 Health Survey. Adolescents with Blount disease ( = 9) were excluded.

Results: Prevalent musculoskeletal and LE pain were reduced by 40% within 12 months and persisted over 3 years. Adjusted models revealed a 6% lower odds of having musculoskeletal pain (odds ratio = 0.94, 95% confidence interval: 0.92-0.99) and a 10% lower odds of having LE pain (odds ratio = 0.90, 95% confidence interval: 0.86-0.95) per 10% reduction of BMI. The prevalence of poor physical function (Health Assessment Questionnaire Disability Index score >0) declined from 49% to <20% at 6 months ( < .05), Physical comfort and the physical component scores, measured by the Impact of Weight on Quality of Life - Kids and the Short Form 36 Health Survey, improved at 6 months postsurgery and beyond ( < .01). Poor physical function predicted persistent joint pain after MBS.

Conclusions: Joint pain, impaired physical function, and impaired health-related quality of life significantly improve after MBS. These benefits in patient-reported outcomes support the use of MBS in adolescents with severe obesity and musculoskeletal pain and suggest that MBS in adolescence may reverse and reduce multiple risk factors for future joint disease.
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http://dx.doi.org/10.1542/peds.2019-1399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889948PMC
December 2019

Football Increases Future Risk of Symptomatic Radiographic Knee Osteoarthritis.

Med Sci Sports Exerc 2020 04;52(4):795-800

Division of Rheumatology, Tufts Medical Center, Boston, MA.

Introduction: Male youth in the United States commonly participate in gridiron (American) football. There are little data substantiating current popular opinion that it is associated with knee pain or osteoarthritis (OA) later in life. We aimed to evaluate the relationship of football with these outcomes in the Osteoarthritis Initiative (OAI).

Methods: This is a study of male OAI participants with knee x-ray readings, symptom assessments, and completed surveys on lifetime physical activity. The OAI is a multicenter, observational cohort recruited from the community not based on football participation status. A history of exposure to American football was ascertained via self-report. Knee radiographs were scored for Kellgren-Lawrence grade (0-4). Radiographic OA (ROA) was defined as Kellgren-Lawrence ≥ 2 in at least one knee. Frequent knee pain meant at least one knee with frequent knee pain. Symptomatic ROA required at least one knee with both ROA and frequent knee pain.

Results: A total of 1166 men had a mean age of 63.7 (SD, 9.2) yr and body mass index of 28.6 (SD, 4.2) kg·m. Thirty-one percent (365/1166) played football at some point in their lives, 95% of whom participated from ages 12 to 18 yr. The ORs for symptomatic ROA from the lowest to highest football participation were 1.2, 1.5, and 2.2, respectively (P for trend = 0.004). Findings were similar for football from ages 12 to 18 yr and for outcomes of knee pain and ROA.

Conclusion: This is the first large epidemiologic study to suggest that football participation, including in the teen years, may be detrimental toward knee health. Prospective studies evaluating football players are warranted.
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http://dx.doi.org/10.1249/MSS.0000000000002189DOI Listing
April 2020

Association of Physical Activity and Fracture Risk Among Postmenopausal Women.

JAMA Netw Open 2019 10 2;2(10):e1914084. Epub 2019 Oct 2.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.

Importance: Physical activity is inversely associated with hip fracture risk in older women. However, the association of physical activity with fracture at other sites and the role of sedentary behavior remain unclear.

Objective: To assess the associations of physical activity and sedentary behavior with fracture incidence among postmenopausal women.

Design, Setting, And Participants: The Women's Health Initiative prospective cohort study enrolled 77 206 postmenopausal women aged 50 to 79 years between October 1993 and December 1998 at 40 US clinical centers. Participants were observed for outcomes through September 2015, with data analysis conducted from June 2017 to August 2019.

Exposures: Self-reported physical activity and sedentary time.

Main Outcomes And Measures: Hazard ratios (HRs) and 95% CIs for total and site-specific fracture incidence.

Results: During a mean (SD) follow-up period of 14.0 (5.2) years among 77 206 women (mean [SD] age, 63.4 [7.3] years; 66 072 [85.6%] white), 25 516 (33.1%) reported a first incident fracture. Total physical activity was inversely associated with the multivariable-adjusted risk of hip fracture (>17.7 metabolic equivalent [MET] h/wk vs none: HR, 0.82; 95% CI, 0.72-0.95; P for trend < .001). Inverse associations with hip fracture were also observed for walking (>7.5 MET h/wk vs none: HR, 0.88; 95% CI, 0.78-0.98; P for trend = .01), mild activity (HR, 0.82; 95% CI, 0.73-0.93; P for trend = .003), moderate to vigorous activity (HR, 0.88; 95% CI, 0.81-0.96; P for trend = .002), and yard work (HR, 0.90; 95% CI, 0.82-0.99; P for trend = .04). Total activity was positively associated with knee fracture (>17.7 MET h/wk vs none: HR, 1.26; 95% CI, 1.05-1.50; P for trend = .08). Mild activity was associated with lower risks of clinical vertebral fracture (HR, 0.87; 95% CI, 0.78-0.96; P for trend = .006) and total fractures (HR, 0.91; 95% CI, 0.87-0.94; P for trend < .001). Moderate to vigorous activity was positively associated with wrist or forearm fracture (HR, 1.09; 95% CI, 1.03-1.15; P for trend = .004). After controlling for covariates and total physical activity, sedentary time was positively associated with total fracture risk (>9.5 h/d vs <6.5 h/d: HR, 1.04; 95% CI, 1.01-1.07; P for trend = .01). When analyzed jointly, higher total activity mitigated some of the total fracture risk associated with sedentary behavior. Analysis of time-varying exposures resulted in somewhat stronger associations for total physical activity, whereas those for sedentary time were materially unchanged.

Conclusions And Relevance: In older ambulatory women, higher total physical activity was associated with lower total and hip fracture risk but higher knee fracture risk. Mild activity and walking were associated with lower hip fracture risk, a finding with important public health implications because these activities are common in older adults. The positive association between sedentary time and total fracture risk requires further investigation.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.14084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822158PMC
October 2019

Evidence that Swimming May Be Protective of Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

PM R 2020 06 4;12(6):529-537. Epub 2019 Dec 4.

Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Background: To date, there have not been any epidemiologic studies that have evaluated the association between swimming over a lifetime and knee health.

Objective: The study aimed to evaluate the relationship of a history of swimming with knee pain, radiographic knee OA (ROA), and symptomatic knee OA (SOA).

Design: Cross-sectional retrospective study.

Setting: Four academic centers in the United States.

Participants: Respondents to the historical physical activity survey within the Osteoarthritis Initiative with knee radiographs and symptom assessments.

Methods: In this retrospective study nested within the Osteoarthritis Initiative, researchers performed logistic regression with the predictor being swimming over a lifetime and over particular age ranges.

Main Outcome Measurements: Person-based definitions of frequent knee pain, ROA, and SOA.

Results: A total of 2637 participants were included, with a mean age of 64.3 years (SD 8.9), body mass index of 28.4 kg/m (SD 4.9), and 44.2% male. Over a lifetime, the adjusted prevalence measures for frequent knee pain, ROA, and SOA for any versus no history of swimming were 36.4% (33.4% - 39.5%) v. 39.9% (37.4% - 42.5%), 54.3% (51.0% - 57.6%) v. 61.1% (58.4% - 63.7%), and 21.9% (19.4% - 24.7%) v. 27.0% (24.7% - 29.4%) respectively.

Conclusions: This is the first epidemiologic study to indicate that swimming is potentially beneficial toward knee health, particularly when performed earlier in life (before age 35). Future prospective studies are needed to confirm these findings and to better scrutinize the associations in older age groups.
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http://dx.doi.org/10.1002/pmrj.12267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166141PMC
June 2020

Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways.

Hum Mol Genet 2020 01;29(1):70-79

Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

We previously identified five single nucleotide polymorphisms (SNPs) at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate two loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5662 cases and 9237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF] = 0.40) was associated with DLBCL risk [odds ratio (OR) = 0.83, P = 3.62 × 10-13]. rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5510 cases and 12 817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF = 0.45) was also associated with DLBCL risk (OR = 1.20, P = 2.31 × 10-12). This SNP is 29 426-bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.
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http://dx.doi.org/10.1093/hmg/ddz228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001601PMC
January 2020

Genome-wide association study of knee pain identifies associations with and in UK Biobank.

Commun Biol 2019 28;2:321. Epub 2019 Aug 28.

1Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.

Knee pain is one of the most common musculoskeletal complaints that brings people to medical attention. Approximately 50% of individuals over the age of 50 report an experience of knee pain within the past 12 months. We sought to identify the genetic variants associated with knee pain in 171,516 subjects from the UK Biobank cohort and seek supporting evidence in cohorts from 23andMe, the Osteoarthritis Initiative, and the Johnston County Osteoarthritis Project. We identified two loci that reached genome-wide significance in the UK Biobank: rs143384, located in ( = 1.32 × 10), a gene previously implicated in osteoarthritis; and rs2808772, located near ( = 1.49 × 10). These findings were supported in cohorts with self-reported osteoarthritis/radiographic knee osteoarthritis without pain information. In this report on genome-wide association of knee pain, we identified two loci in or near and that are associated with knee pain.
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http://dx.doi.org/10.1038/s42003-019-0568-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713725PMC
April 2020
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