Publications by authors named "Thomas J Hoffmann"

88 Publications

The Space in the Middle: Attitudes of Women's Health and Neonatal Nurses in the United States about Abortion.

Womens Health Issues 2021 Nov 26. Epub 2021 Nov 26.

University of California, San Francisco School of Nursing and the ACTIONS Program, San Francisco, California.

Introduction: Despite playing an integral part in sexual and reproductive health care, including abortion care, nurses are rarely the focus of research regarding their attitudes about abortion.

Methods: A sample of 1,820 nurse members of the Association of Women's Health, Obstetric, and Neonatal Nurses were surveyed about their demographic and professional backgrounds, religious beliefs, and abortion attitudes. Scores on the Abortion Attitudes Scale were analyzed categorically and trichotomized in multinomial regression analyses.

Results: Almost one-third of the sample (32%) had moderately proabortion attitudes, 29% were unsure, 16% had strongly proabortion attitudes, 13% had strongly antiabortion attitudes, and 11% had moderately antiabortion attitudes. Using trichotomized Abortion Attitudes Scale scores (proabortion, unsure, antiabortion), adjusted regression models showed that the following characteristics were associated with proabortion attitudes: being non-Christian, residence in the North or West, having no children, and having had an abortion.

Conclusions: Understanding nurses' attitudes toward abortion, and what characteristics may influence their attitudes, is critical to sustaining nursing care for patients considering and seeking abortion. Additionally, because personal characteristics were associated with antiabortion attitudes, it is likely that personal experiences may influence attitudes toward abortion. A large percentage of nurses held attitudes that placed them in the "unsure" category. Given the current ubiquitous polarization of abortion discourse, this finding indicates that the binary narrative of this topic is less pervasive than expected, which lends itself to an emphasis on empathetic and compassionate nursing care.
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http://dx.doi.org/10.1016/j.whi.2021.10.011DOI Listing
November 2021

New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis.

Commun Biol 2021 07 22;4(1):864. Epub 2021 Jul 22.

Sutter Health, Walnut Creek, CA, USA.

Migraine is a common disabling primary headache disorder that is ranked as the most common neurological cause of disability worldwide. Women present with migraine much more frequently than men, but the reasons for this difference are unknown. Migraine heritability is estimated to up to 57%, yet much of the genetic risk remains unaccounted for, especially in non-European ancestry populations. To elucidate the etiology of this common disorder, we conduct a multiethnic genome-wide association meta-analysis of migraine, combining results from the GERA and UK Biobank cohorts, followed by a European-ancestry meta-analysis using public summary statistics. We report 79 loci associated with migraine, of which 45 were novel. Sex-stratified analyses identify three additional novel loci (CPS1, PBRM1, and SLC25A21) specific to women. This large multiethnic migraine study provides important information that may substantially improve our understanding of the etiology of migraine susceptibility.
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http://dx.doi.org/10.1038/s42003-021-02356-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298472PMC
July 2021

Coffee Consumption and Incident Tachyarrhythmias: Reported Behavior, Mendelian Randomization, and Their Interactions.

JAMA Intern Med 2021 Sep;181(9):1185-1193

Division of Cardiology, University of California, San Francisco, San Francisco.

Importance: The notion that caffeine increases the risk of cardiac arrhythmias is common. However, evidence that the consumption of caffeinated products increases the risk of arrhythmias remains poorly substantiated.

Objective: To assess the association between consumption of common caffeinated products and the risk of arrhythmias.

Design, Setting, And Participants: This prospective cohort study analyzed longitudinal data from the UK Biobank between January 1, 2006, and December 31, 2018. After exclusion criteria were applied, 386 258 individuals were available for analyses.

Exposures: Daily coffee intake and genetic polymorphisms that affect caffeine metabolism.

Main Outcomes And Measures: Any cardiac arrhythmia, including atrial fibrillation or flutter, supraventricular tachycardia, ventricular tachycardia, premature atrial complexes, and premature ventricular complexes.

Results: A total of 386 258 individuals (mean [SD] age, 56 [8] years; 52.3% female) were assessed. During a mean (SD) follow-up of 4.5 (3.1) years, 16 979 participants developed an incident arrhythmia. After adjustment for demographic characteristics, comorbid conditions, and lifestyle habits, each additional cup of habitual coffee consumed was associated with a 3% lower risk of incident arrhythmia (hazard ratio [HR], 0.97; 95% CI, 0.96-0.98; P < .001). In analyses of each arrhythmia alone, statistically significant associations exhibiting a similar magnitude were observed for atrial fibrillation and/or flutter (HR, 0.97; 95% CI, 0.96-0.98; P < .001) and supraventricular tachycardia (HR, 0.96; 95% CI, 0.94-0.99; P = .002). Two distinct interaction analyses, one using a caffeine metabolism-related polygenic score of 7 genetic polymorphisms and another restricted to CYP1A2 rs762551 alone, did not reveal any evidence of effect modification. A mendelian randomization study that used these same genetic variants revealed no significant association between underlying propensities to differing caffeine metabolism and the risk of incident arrhythmia.

Conclusions And Relevance: In this prospective cohort study, greater amounts of habitual coffee consumption were associated with a lower risk of arrhythmia, with no evidence that genetically mediated caffeine metabolism affected that association. Mendelian randomization failed to provide evidence that caffeine consumption was associated with arrhythmias.
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http://dx.doi.org/10.1001/jamainternmed.2021.3616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290332PMC
September 2021

A unified framework identifies new links between plasma lipids and diseases from electronic medical records across large-scale cohorts.

Nat Genet 2021 07 17;53(7):972-981. Epub 2021 Jun 17.

Department of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Plasma lipids are known heritable risk factors for cardiovascular disease, but increasing evidence also supports shared genetics with diseases of other organ systems. We devised a comprehensive three-phase framework to identify new lipid-associated genes and study the relationships among lipids, genotypes, gene expression and hundreds of complex human diseases from the Electronic Medical Records and Genomics (347 traits) and the UK Biobank (549 traits). Aside from 67 new lipid-associated genes with strong replication, we found evidence for pleiotropic SNPs/genes between lipids and diseases across the phenome. These include discordant pleiotropy in the HLA region between lipids and multiple sclerosis and putative causal paths between triglycerides and gout, among several others. Our findings give insights into the genetic basis of the relationship between plasma lipids and diseases on a phenome-wide scale and can provide context for future prevention and treatment strategies.
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http://dx.doi.org/10.1038/s41588-021-00879-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555954PMC
July 2021

A large multiethnic GWAS meta-analysis of cataract identifies new risk loci and sex-specific effects.

Nat Commun 2021 06 14;12(1):3595. Epub 2021 Jun 14.

Kaiser Permanente Northern California (KPNC), Division of Research, Oakland, CA, USA.

Cataract is the leading cause of blindness among the elderly worldwide and cataract surgery is one of the most common operations performed in the United States. As the genetic etiology of cataract formation remains unclear, we conducted a multiethnic genome-wide association meta-analysis, combining results from the GERA and UK Biobank cohorts, and tested for replication in the 23andMe research cohort. We report 54 genome-wide significant loci, 37 of which were novel. Sex-stratified analyses identified CASP7 as an additional novel locus specific to women. We show that genes within or near 80% of the cataract-associated loci are significantly expressed and/or enriched-expressed in the mouse lens across various spatiotemporal stages as per iSyTE analysis. Furthermore, iSyTE shows 32 candidate genes in the associated loci have altered gene expression in 9 different gene perturbation mouse models of lens defects/cataract, suggesting their relevance to lens biology. Our work provides further insight into the complex genetic architecture of cataract susceptibility.
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http://dx.doi.org/10.1038/s41467-021-23873-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203611PMC
June 2021

Effect of SLCO1B1 T521C on Statin-Related Myotoxicity With Use of Lovastatin and Atorvastatin.

Clin Pharmacol Ther 2021 09 23;110(3):733-740. Epub 2021 Jul 23.

Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California, USA.

The association between the c.521T>C variant allele in SLCO1B1 (reference single nucleotide polymorphism (rs)4149056) and simvastatin-induced myotoxicity was discovered over a decade ago; however, whether this relationship represents a class effect is still not fully known. The aim of this study was to investigate the relationship between rs4149056 genotype and statin-induced myotoxicity in patients taking atorvastatin and lovastatin. Study participants were from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. A total of 233 statin-induced myopathy + rhabdomyolysis cases met the criteria for inclusion and were matched to 2,342 controls. To validate the drug response phenotype, we replicated the previously established association between rs4149056 genotype and simvastatin-induced myotoxicity. In particular, compared with homozygous T allele carriers, there was a significantly increased risk of simvastatin-induced myopathy + rhabdomyolysis in homozygous carriers of the C allele (CC vs. TT, odds ratio [OR] 4.62, 95% confidence interval [CI] 1.58-11.90, P = 0.003). For lovastatin users, homozygous carriers of the C allele were also at increased risk of statin-induced myopathy + rhabdomyolysis (CC vs. TT, OR 4.49, 95% CI 1.68-10.80, P = 0.001). In atorvastatin users, homozygous carriers of the C allele were twice as likely to experience statin-induced myopathy, though this association did not achieve statistical significance (CC vs. TT, OR 2.00, 95% CI 0.44-6.59, P = 0.30). In summary, our findings suggest that the association of rs4149056 with simvastatin-related myotoxicity may also extend to lovastatin. More data is needed to determine the extent of the association in atorvastatin users. Altogether, these data expand the evidence base for informing guidelines of pharmacogenetic-based statin prescribing practices.
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http://dx.doi.org/10.1002/cpt.2337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376784PMC
September 2021

Examining the relationship between interpersonal support and retention in HIV care among HIV+ nursing mothers in Uganda.

BMC Res Notes 2021 Jun 3;14(1):224. Epub 2021 Jun 3.

Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.

Objective: The global burden of HIV on women and pediatric populations are severe in sub-Saharan Africa. Global child HIV infection rates have declined, but this rate remains quite high in sub-Saharan Africa due to Mother-to-child transmission (MTCT). To prevent MTCT of HIV, postpartum women living with HIV (WLHIV) are required to return to a health facility for HIV care within 60 days after childbirth (Retention in HIV care). Studies suggest that interpersonal support was positively associated with retention in HIV care. However, information on this association is lacking among postpartum WLHIV in Uganda. Therefore, this study investigates the relationship between interpersonal support, measured with the Interpersonal Support Evaluation List (ISEL-12), and retention in HIV care.

Results: In a total of 155 postpartum WLHIV, 84% were retained in HIV care. ISEL-12 was negatively associated with retention in HIV care. Postpartum WLHIV retained in care (24.984 ± 4.549) have lower ISEL-12 scores compared to the non-retained group (27.520 ± 4.224), t(35.572) = - 2.714, p = 0.01. In the non-income earning sample, respondents retained in care (24.110 ± 4.974) have lower ISEL scores compared to the non-retained group (27.000 ± 4.855), t(20.504) = -2.019, p = 0.049. This was not significant among income earning WLHIV.
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http://dx.doi.org/10.1186/s13104-021-05639-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176692PMC
June 2021

Mobile Health Intervention Promoting Physical Activity in Adults Post Cardiac Rehabilitation: Pilot Randomized Controlled Trial.

JMIR Form Res 2021 Apr 16;5(4):e20468. Epub 2021 Apr 16.

Departments of Medicine and Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, United States.

Background: Cardiac rehabilitation (CR) is an exercise-based program prescribed after cardiac events associated with improved physical, mental, and social functioning; however, many patients return to a sedentary lifestyle leading to deteriorating functional capacity after discharge from CR. Physical activity (PA) is critical to avoid recurrence of cardiac events and mortality and maintain functional capacity. Leveraging mobile health (mHealth) strategies to increase adherence to PA is a promising approach. Based on the social cognitive theory, we sought to determine whether mHealth strategies (Movn mobile app for self-monitoring, supportive push-through messages, and wearable activity tracker) would improve PA and functional capacity over 2 months.

Objective: The objectives of this pilot randomized controlled trial were to examine preliminary effects of an mHealth intervention on group differences in PA and functional capacity and group differences in depression and self-efficacy to maintain exercise after CR.

Methods: During the final week of outpatient CR, patients were randomized 1:1 to the intervention group or usual care. The intervention group downloaded the Movn mobile app, received supportive push-through messages on motivation and educational messages related to cardiovascular disease (CVD) management 3 times per week, and wore a Charge 2 (Fitbit Inc) activity tracker to track step counts. Participants in the usual care group wore a pedometer and recorded their daily steps in a diary. Data from the 6-minute walk test (6MWT) and self-reported questionnaires were collected at baseline and 2 months.

Results: We recruited 60 patients from 2 CR sites at a community hospital in Northern California. The mean age was 68.0 (SD 9.3) years, and 23% (14/60) were female; retention rate was 85% (51/60). Our results from 51 patients who completed follow-up showed the intervention group had a statistically significant higher mean daily step count compared with the control (8860 vs 6633; P=.02). There was no difference between groups for the 6MWT, depression, or self-efficacy to maintain exercise.

Conclusions: This intervention addresses a major public health initiative to examine the potential for mobile health strategies to promote PA in patients with CVD. Our technology-based pilot mHealth intervention provides promising results on a pragmatic and contemporary approach to promote PA by increasing daily step counts after completing CR.

Trial Registration: ClinicalTrials.gov NCT03446313; https://clinicaltrials.gov/ct2/show/NCT03446313.
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http://dx.doi.org/10.2196/20468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087971PMC
April 2021

Extension of Mendelian Randomization to Identify Earliest Manifestations of Alzheimer Disease: Association of Genetic Risk Score for Alzheimer Disease With Lower Body Mass Index by Age 50 Years.

Am J Epidemiol 2021 10;190(10):2163-2171

Weight loss or lower body mass index (BMI) could be an early symptom of Alzheimer disease (AD), but when this begins to emerge is difficult to estimate with traditional observational data. In an extension of Mendelian randomization, we leveraged variation in genetic risk for late-onset AD risk to estimate the causal effect of AD on BMI and the earliest ages at which AD-related weight loss (or lower BMI as a proxy) occurs. We studied UK Biobank participants enrolled in 2006-2010, who were without dementia, aged 39-73, with European genetic ancestry. BMI was calculated with measured height/weight (weight (kg)/height (m)2). An AD genetic risk score (AD-GRS) was calculated based on 23 genetic variants. Using linear regressions, we tested the association of AD-GRS with BMI, stratified by decade, and calculated the age of divergence in BMI trends between low and high AD-GRS. AD-GRS was not associated with BMI in 39- to 49-year-olds (β = 0.00, 95% confidence interval (CI): -0.03, 0.03). AD-GRS was associated with lower BMI in 50- to 59-year-olds (β = -0.03, 95% CI: -0.06, -0.01) and 60- to 73-year-olds (β = -0.09, 95% CI:-0.12, -0.07). Model-based BMI age curves for high versus low AD-GRS began to diverge after age 47 years. Sensitivity analyses found no evidence for pleiotropy or survival bias. Longitudinal replication is needed; however, our findings suggest that AD genes might begin to reduce BMI decades prior to dementia diagnosis.
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http://dx.doi.org/10.1093/aje/kwab103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576370PMC
October 2021

Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts.

Nat Commun 2021 02 12;12(1):970. Epub 2021 Feb 12.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PRS is evaluated in multivariable logistic regression models against all other cancer types. Results are then meta-analyzed across cohorts. Ten positive and one inverse cross-cancer associations are found after multiple testing correction. Two pairs show bidirectional associations; the melanoma PRS is positively associated with oral cavity/pharyngeal cancer and vice versa, whereas the lung cancer PRS is positively associated with oral cavity/pharyngeal cancer, and the oral cavity/pharyngeal cancer PRS is inversely associated with lung cancer. Overall, we validate known, and uncover previously unreported, patterns of pleiotropy that have the potential to inform investigations of risk prediction, shared etiology, and precision cancer prevention strategies.
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http://dx.doi.org/10.1038/s41467-021-21288-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880989PMC
February 2021

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Nat Genet 2021 01 4;53(1):65-75. Epub 2021 Jan 4.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
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http://dx.doi.org/10.1038/s41588-020-00748-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148035PMC
January 2021

Genetic ancestry, skin pigmentation, and the risk of cutaneous squamous cell carcinoma in Hispanic/Latino and non-Hispanic white populations.

Commun Biol 2020 12 14;3(1):765. Epub 2020 Dec 14.

Department of Dermatology, Massachusetts General Hospital, Boston, MA, 02114, USA.

Although cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in individuals of European ancestry, the incidence of cSCC in Hispanic/Latinos is also increasing. cSCC has both a genetic and environmental etiology. Here, we examine the role of genetic ancestry, skin pigmentation, and sun exposure in Hispanic/Latinos and non-Hispanic whites on cSCC risk. We observe an increased cSCC risk with greater European ancestry (P = 1.27 × 10) within Hispanic/Latinos and with greater northern (P = 2.38 × 10) and western (P = 2.28 × 10) European ancestry within non-Hispanic whites. These associations are significantly, but not completely, attenuated after considering skin pigmentation-associated loci, history of actinic keratosis, and sun-protected versus sun-exposed anatomical sites. We also report an association of the well-known pigment variant Ala111Thr (rs1426654) at SLC24A5 with cSCC in Hispanic/Latinos. These findings demonstrate a strong correlation of northwestern European genetic ancestry with cSCC risk in both Hispanic/Latinos and non-Hispanic whites, largely but not entirely mediated through its impact on skin pigmentation.
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http://dx.doi.org/10.1038/s42003-020-01461-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736583PMC
December 2020

A Large-Scale Association Study Detects Novel Rare Variants, Risk Genes, Functional Elements, and Polygenic Architecture of Prostate Cancer Susceptibility.

Cancer Res 2021 04 8;81(7):1695-1703. Epub 2020 Dec 8.

Program in Biological and Medical Informatics, University of California San Francisco, San Francisco, California.

To identify rare variants associated with prostate cancer susceptibility and better characterize the mechanisms and cumulative disease risk associated with common risk variants, we conducted an integrated study of prostate cancer genetic etiology in two cohorts using custom genotyping microarrays, large imputation reference panels, and functional annotation approaches. Specifically, 11,984 men (6,196 prostate cancer cases and 5,788 controls) of European ancestry from Northern California Kaiser Permanente were genotyped and meta-analyzed with 196,269 men of European ancestry (7,917 prostate cancer cases and 188,352 controls) from the UK Biobank. Three novel loci, including two rare variants (European ancestry minor allele frequency < 0.01, at 3p21.31 and 8p12), were significant genome wide in a meta-analysis. Gene-based rare variant tests implicated a known prostate cancer gene (), as well as a novel candidate gene (), which encodes a receptor highly expressed in prostate tissue and is related to the B7/CD28 family of T-cell immune checkpoint markers. Haplotypic patterns of long-range linkage disequilibrium were observed for rare genetic variants at and other loci, reflecting their evolutionary history. In addition, a polygenic risk score (PRS) of 188 prostate cancer variants was strongly associated with risk (90th vs. 40th-60th percentile OR = 2.62, = 2.55 × 10). Many of the 188 variants exhibited functional signatures of gene expression regulation or transcription factor binding, including a 6-fold difference in log-probability of androgen receptor binding at the variant rs2680708 (17q22). Rare variant and PRS associations, with concomitant functional interpretation of risk mechanisms, can help clarify the full genetic architecture of prostate cancer and other complex traits. SIGNIFICANCE: This study maps the biological relationships between diverse risk factors for prostate cancer, integrating different functional datasets to interpret and model genome-wide data from over 200,000 men with and without prostate cancer..
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137514PMC
April 2021

Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.

Nat Commun 2020 09 4;11(1):4423. Epub 2020 Sep 4.

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.

Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.
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http://dx.doi.org/10.1038/s41467-020-18246-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473862PMC
September 2020

Association of genetic risk for Alzheimer disease and hearing impairment.

Neurology 2020 10 2;95(16):e2225-e2234. Epub 2020 Sep 2.

From the Department of Psychiatry and Behavioral Sciences (W.D.B., K.Y.), Department of Epidemiology and Biostatistics (K.Y., S.F.A., T.J.H., M.M.G.), Department of Neurology (K.Y.), and Institute for Human Genetics (T.J.H.), University of California, San Francisco; 23andMe (T.J.F.), Mountain View; San Francisco VA Health Care System (K.Y.), CA; Department of Medicine and Public Health (S.W.), Rey Juan Carlos University, Madrid, Spain; Kaiser Permanente Northern California Division of Research (E.J.), Oakland; and Public Health Sciences (R.A.W.), Division of Epidemiology, Alzheimer's Disease Research Center, UC Davis School of Medicine, CA.

Objective: To test the hypothesis that incipient Alzheimer disease (AD) may adversely affect hearing and that hearing loss may adversely affect cognition, we evaluated whether genetic variants that increase AD risk also increase problem hearing and genetic variants that increase hearing impairment risk do not influence cognition.

Methods: UK Biobank participants without dementia ≥56 years of age with Caucasian genetic ancestry completed a Digit Triplets Test of speech-in-noise hearing (n = 80,074), self-reported problem hearing and hearing with background noise (n = 244,915), and completed brief cognitive assessments. A genetic risk score for AD (AD-GRS) was calculated as a weighted sum of 23 previously identified AD-related polymorphisms. A genetic risk score for hearing (hearing-GRS) was calculated using 3 previously identified polymorphisms related to hearing impairment. Using age-, sex-, and genetic ancestry-adjusted logistic and linear regression models, we evaluated whether the AD-GRS predicted poor hearing and whether the hearing-GRS predicted worse cognition.

Results: Poor speech-in-noise hearing (>-5.5-dB speech reception threshold; prevalence 14%) was associated with lower cognitive scores (ß = -1.28; 95% confidence interval [CI] -1.54 to -1.03). Higher AD-GRS was significantly associated with poor speech-in-noise hearing (odds ratio [OR] 1.06; 95% CI 1.01-1.11) and self-reported problems hearing with background noise (OR 1.03; 95% CI 1.00-1.05). Hearing-GRS was not significantly associated with cognitive scores (ß = -0.05; 95% CI -0.17 to 0.07).

Conclusions: Genetic risk for AD also influences speech-in-noise hearing. We failed to find evidence that genetic risk for hearing impairment affects cognition. AD disease processes or a that shared etiology may cause speech-in-noise difficulty before dementia onset.
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http://dx.doi.org/10.1212/WNL.0000000000010709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713783PMC
October 2020

Association of HIV infection with clinical and laboratory characteristics of sickle cell disease.

BMC Infect Dis 2020 Aug 27;20(1):638. Epub 2020 Aug 27.

University of California, San Francisco (UCSF), San Francisco, CA, USA.

Background: Sickle cell disease (SCD) is a multisystem disorder characterized by a wide spectrum of clinical manifestations and severity. Studies investigating potential effects of co-morbid human immunodeficiency virus (HIV) and SCD have produced conflicting results, and additional investigations are needed to elucidate whether the interaction between the two disease states might impact both HIV and SCD clinical outcomes. The association of HIV infection with clinical and laboratory characteristics of patients with SCD was assessed.

Methods: This nested case-control study included individuals with SCD with HIV treated at six Brazilian SCD centers. Clinical and laboratory data were abstracted from medical records. HIV positive participants were compared to age, gender, center, and SCD genotype matched HIV negative participants (ratio 1:4). Individual clinical outcomes as well as a composite outcome of any SCD complication and a composite outcome of any HIV-related complication were compared between the two groups.

Results: Fifteen HIV positive participants were included, 12 (80%) alive and 3 (20%) deceased. Most of the HIV positive patients had HbSS (60%; n = 9), 53% (n = 8) were female, and mean age was 30 ± 13 years. The frequency of individual SCD complications of acute chest syndrome/pneumonia, sepsis/bacteremia, pyelonephritis, ischemic stroke, hemorrhagic stroke, abnormal transcranial Doppler (TCD), and pulmonary hypertension was higher in HIV positive participants when compared to HIV negative, although analyzed individually none were statistically significant. HIV positive participants had significantly higher risk of any SCD complication and of a composite HIV-related complication compared to the HIV negative group (HR = 4.6; 95%CI 1.1-19.6; P = 0.04 and HR = 7.7; 95%CI 1.5-40.2; P = 0.02, respectively). There was a non-significant trend towards higher risk of any infections in participants with HIV positive (HR = 3.5; 95%CI 0.92-13.4; P = 0.07). Laboratory parameters levels were not significantly different in individuals with and without HIV.

Conclusions: In summary, our study in SCD patients shows that those with HIV have an increased risk of any SCD complication and HIV-related complications, as well as a suggestive but not significantly increased risk of infections.
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http://dx.doi.org/10.1186/s12879-020-05366-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457248PMC
August 2020

Attitudes of California Registered Nurses About Abortion.

J Obstet Gynecol Neonatal Nurs 2020 09 9;49(5):475-486. Epub 2020 Aug 9.

Objective: To describe attitudes about abortion among registered nurses (RNs) licensed in California and to determine if demographic characteristics were associated with these attitudes.

Design: Cross-sectional, one-time survey.

Setting: Online between 2015 and 2017.

Participants: Nurses with active RN licenses in California (N = 2,500).

Methods: An anonymous survey was sent to a random sample of 2,500 RNs with active California licenses between 2015 and 2017 to assess their personal and professional demographic characteristics and their attitudes toward abortion. Using scores on the Abortion Attitudes Scale, we dichotomized participants into proabortion and antiabortion categories. We used chi-square tests to determine differences based on demographic characteristics.

Results: Data from 504 RNs licensed in California are included in this analysis. Most respondents identified as female (n = 462, 92%), older than 50 years of age (n = 379, 75%), married (n = 364, 72%), White (n = 354, 70%), and Christian (n = 322, 64%). They were more likely to have negative attitudes toward abortion care if they identified as Christian (p < .001) and more positive attitudes if they identified as White (p < .001) independent of identifying as Christian.

Conclusions: Respondents had a complex range of attitudes about abortion. In some cases, these attitudes aligned and/or conflicted with stated religious orientation. This study highlights the demographic characteristics that are associated with the attitudes and beliefs about abortion among RNs licensed in California.
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http://dx.doi.org/10.1016/j.jogn.2020.06.005DOI Listing
September 2020

Meta-Analysis of 26 638 Individuals Identifies Two Genetic Loci Associated With Left Ventricular Ejection Fraction.

Circ Genom Precis Med 2020 08 30;13(4):e002804. Epub 2020 Jun 30.

Division of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA (H.C., K.K.T., C.J., D.K.R., A.S.G., N.R., C.S.).

Background: Left ventricular ejection fraction (EF) is an indicator of cardiac function, usually assessed in individuals with heart failure and other cardiac conditions. Although family studies indicate that EF has an important genetic component with heritability estimates up to 0.61, to date only 6 EF-associated loci have been reported.

Methods: Here, we conducted a genome-wide association study (GWAS) of EF in 26 638 adults from the Genetic Epidemiology Research on Adult Health and Aging and the UK Biobank cohorts.

Results: A meta-analysis combining results from Genetic Epidemiology Research on Adult Health and Aging and UK Biobank identified a novel locus: on chromosome 3p25 (rs11719526; β=0.47 and =3.10×10) that replicated in Biobank Japan and confirmed recent findings implicating the locus on chromosome 10q26 in EF variation, with the strongest association observed for rs17617337 (β=-0.83 and =8.24×10). Although the minor allele frequencies of rs11719526 were generally common (between 0.13 and 0.44) in different ethnic groups, rs17617337 was rare (minor allele frequencies<0.05) in Asian and African ancestry populations. These associations were slightly attenuated, after considering antecedent cardiac conditions (ie, heart failure/cardiomyopathy, hypertension, myocardial infarction, atrial fibrillation, valvular disease, and revascularization procedures). This suggests that the effects of the lead variants at or on EF are largely independent of these conditions.

Conclusions: In this large and multiethnic study, we identified 2 loci, and , associated with EF at a genome-wide significance level. Identifying and understanding the genetic determinants of EF is important to better understand the pathophysiology of this strong correlate of cardiac outcomes and to help target the development of future therapies.
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http://dx.doi.org/10.1161/CIRCGEN.119.002804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446727PMC
August 2020

A multiethnic genome-wide analysis of 44,039 individuals identifies 41 new loci associated with central corneal thickness.

Commun Biol 2020 06 11;3(1):301. Epub 2020 Jun 11.

Kaiser Permanente Northern California (KPNC), Division of Research, Oakland, CA, 94612, USA.

Central corneal thickness (CCT) is one of the most heritable human traits, with broad-sense heritability estimates ranging between 0.68 to 0.95. Despite the high heritability and numerous previous association studies, only 8.5% of CCT variance is currently explained. Here, we report the results of a multiethnic meta-analysis of available genome-wide association studies in which we find association between CCT and 98 genomic loci, of which 41 are novel. Among these loci, 20 were significantly associated with keratoconus, and one (RAPSN rs3740685) was significantly associated with glaucoma after Bonferroni correction. Two-sample Mendelian randomization analysis suggests that thinner CCT does not causally increase the risk of primary open-angle glaucoma. This large CCT study explains up to 14.2% of CCT variance and increases substantially our understanding of the etiology of CCT variation. This may open new avenues of investigation into human ocular traits and their relationship to the risk of vision disorders.
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http://dx.doi.org/10.1038/s42003-020-1037-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289804PMC
June 2020

Analysis of putative cis-regulatory elements regulating blood pressure variation.

Hum Mol Genet 2020 07;29(11):1922-1932

Department of Genetic Medicine, McKusick-Nathans Institute, Baltimore, MD 21205, USA.

Hundreds of loci have been associated with blood pressure (BP) traits from many genome-wide association studies. We identified an enrichment of these loci in aorta and tibial artery expression quantitative trait loci in our previous work in ~100 000 Genetic Epidemiology Research on Aging study participants. In the present study, we sought to fine-map known loci and identify novel genes by determining putative regulatory regions for these and other tissues relevant to BP. We constructed maps of putative cis-regulatory elements (CREs) using publicly available open chromatin data for the heart, aorta and tibial arteries, and multiple kidney cell types. Variants within these regions may be evaluated quantitatively for their tissue- or cell-type-specific regulatory impact using deltaSVM functional scores, as described in our previous work. We aggregate variants within these putative CREs within 50 Kb of the start or end of 'expressed' genes in these tissues or cell types using public expression data and use deltaSVM scores as weights in the group-wise sequence kernel association test to identify candidates. We test for association with both BP traits and expression within these tissues or cell types of interest and identify the candidates MTHFR, C10orf32, CSK, NOV, ULK4, SDCCAG8, SCAMP5, RPP25, HDGFRP3, VPS37B and PPCDC. Additionally, we examined two known QT interval genes, SCN5A and NOS1AP, in the Atherosclerosis Risk in Communities Study, as a positive control, and observed the expected heart-specific effect. Thus, our method identifies variants and genes for further functional testing using tissue- or cell-type-specific putative regulatory information.
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http://dx.doi.org/10.1093/hmg/ddaa098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372556PMC
July 2020

The impact of adjusting for baseline in pharmacogenomic genome-wide association studies of quantitative change.

NPJ Genom Med 2020 16;5. Epub 2020 Jan 16.

2Institute for Human Genetics, University of California, San Francisco, CA 94143 USA.

In pharmacogenomic studies of quantitative change, any association between genetic variants and the pretreatment (baseline) measurement can bias the estimate of effect between those variants and drug response. A putative solution is to adjust for baseline. We conducted a series of genome-wide association studies (GWASs) for low-density lipoprotein cholesterol (LDL-C) response to statin therapy in 34,874 participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort as a case study to investigate the impact of baseline adjustment on results generated from pharmacogenomic studies of quantitative change. Across phenotypes of statin-induced LDL-C change, baseline adjustment identified variants from six loci meeting genome-wide significance (, and /). In contrast, baseline-unadjusted analyses yielded variants from three loci meeting the criteria for genome-wide significance (, , and ). A genome-wide heterogeneity test of baseline versus statin on-treatment LDL-C levels was performed as the definitive test for the true effect of genetic variants on statin-induced LDL-C change. These findings were generally consistent with the models not adjusting for baseline signifying that genome-wide significant hits generated only from baseline-adjusted analyses (/) were likely biased. We then comprehensively reviewed published GWASs of drug-induced quantitative change and discovered that more than half (59%) inappropriately adjusted for baseline. Altogether, we demonstrate that (1) baseline adjustment introduces bias in pharmacogenomic studies of quantitative change and (2) this erroneous methodology is highly prevalent. We conclude that it is critical to avoid this common statistical approach in future pharmacogenomic studies of quantitative change.
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http://dx.doi.org/10.1038/s41525-019-0109-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965183PMC
January 2020

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

JAMA 2019 11;322(17):1682-1691

Clayton Eye Care Center Management Inc, Marrow, Georgia.

Importance: Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders.

Objectives: To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma.

Design, Settings, And Participants: A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma.

Exposures: Genetic variants associated with primary open-angle glaucoma.

Main Outcomes And Measures: Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data.

Results: A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry.

Conclusions And Relevance: In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies.
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http://dx.doi.org/10.1001/jama.2019.16161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865235PMC
November 2019

Author Correction: Association of imputed prostate cancer transcriptome with disease risk reveals novel mechanisms.

Nat Commun 2019 Aug 28;10(1):3948. Epub 2019 Aug 28.

Program in Biological and Medical Informatics, University of California San Francisco, San Francisco, CA, 94158, USA.

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/s41467-019-11810-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713745PMC
August 2019

Genetic ancestry does not explain increased atopic dermatitis susceptibility or worse disease control among African American subjects in 2 large US cohorts.

J Allergy Clin Immunol 2020 01 29;145(1):192-198.e11. Epub 2019 Jul 29.

Division of Research, Kaiser Permanente, Oakland, Calif.

Background: Atopic dermatitis (AD) is more common among African American children. Whether there are racial/ethnic difference among adults with AD and the causes for those disparities are unclear.

Objective: We sought to examine the relationship between self-reported race/ethnicity and AD and determine whether African genetic ancestry is predictive of these outcomes among African American subjects.

Methods: We analyzed data from 2 independent multiethnic longitudinal studies: 86,893 subjects aged 18 to 100 years from the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort and 5467 subjects aged 2 to 26 years from the national Pediatric Eczema Elective Registry (PEER) cohort. The primary outcomes were physician-diagnosed AD in GERA and repeated measures of self-reported disease control among patients with physician-diagnosed AD at 6-month intervals in PEER. We examined whether self-identified African American race/ethnicity was predictive of these outcomes and then tested whether a continuous measure of African genetic ancestry was associated with outcomes within the African American group.

Results: AD was more common among self-identified African American subjects than non-Hispanic white subjects in GERA (4.4% vs 2.1%; odds ratio, 2.06; 95% CI, 1.70-2.48) and less well-controlled in PEER subjects (odds of 1-level worse control, 1.91; 95% CI, 1.64-2.22). However, African genetic ancestry was not associated with AD risk or control among self-identified African American subjects in either cohort, nor did an AD polygenic risk score or genetic skin pigment score explain the AD disparities in patients with AD.

Conclusion: Ancestry-related genetic effects do not explain increased AD prevalence or poorer disease control among African American subjects.
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http://dx.doi.org/10.1016/j.jaci.2019.06.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949407PMC
January 2020

Association of imputed prostate cancer transcriptome with disease risk reveals novel mechanisms.

Nat Commun 2019 07 15;10(1):3107. Epub 2019 Jul 15.

Program in Biological and Medical Informatics, University of California San Francisco, San Francisco, CA, 94158, USA.

Here we train cis-regulatory models of prostate tissue gene expression and impute expression transcriptome-wide for 233,955 European ancestry men (14,616 prostate cancer (PrCa) cases, 219,339 controls) from two large cohorts. Among 12,014 genes evaluated in the UK Biobank, we identify 38 associated with PrCa, many replicating in the Kaiser Permanente RPGEH. We report the association of elevated TMPRSS2 expression with increased PrCa risk (independent of a previously-reported risk variant) and with increased tumoral expression of the TMPRSS2:ERG fusion-oncogene in The Cancer Genome Atlas, suggesting a novel germline-somatic interaction mechanism. Three novel genes, HOXA4, KLK1, and TIMM23, additionally replicate in the RPGEH cohort. Furthermore, 4 genes, MSMB, NCOA4, PCAT1, and PPP1R14A, are associated with PrCa in a trans-ethnic meta-analysis (N = 9117). Many genes exhibit evidence for allele-specific transcriptional activation by PrCa master-regulators (including androgen receptor) in Position Weight Matrix, Chip-Seq, and Hi-C experimental data, suggesting common regulatory mechanisms for the associated genes.
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http://dx.doi.org/10.1038/s41467-019-10808-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629701PMC
July 2019

Rare Protein-Altering Telomere-related Gene Variants in Patients with Chronic Hypersensitivity Pneumonitis.

Am J Respir Crit Care Med 2019 11;200(9):1154-1163

Department of Medicine.

Rare genetic variants in telomere-related genes have been identified in familial, idiopathic, and rheumatoid arthritis-associated pulmonary fibrosis. Short peripheral blood leukocyte (PBL) telomere length predicts poor outcomes in chronic hypersensitivity pneumonitis (CHP). Determine the prevalence and clinical relevance of rare protein-altering variants in telomere-related genes in patients with CHP. Next-generation sequences from two CHP cohorts were analyzed to identify variants in (telomerase reverse transcriptase), (telomerase RNA component), (dyskerin pseudouridine synthase 1), (regulator of telomere elongation helicase 1), (poly[A]-specific RNase), and (TERF1-interacting nuclear factor 2). To qualify, variants were required to have a minor allele frequency less than 0.005 and be predicted to be damaging to protein function. Variant status (binary variable) was used in statistical association tests, including Cox proportional hazard models for transplant-free survival. PBL telomere length was measured using quantitative PCR. Qualifying variants were identified in 16 of 144 patients (11.1%; 95% confidence interval [CI], 6.5-17.4) in the discovery cohort and 17 of 209 patients (8.1%; 95% CI, 4.8-12.7) in the replication cohort. Age- and ancestry-adjusted PBL telomere length was significantly shorter in the presence of a variant in both cohorts (discovery: -561 bp; 95% CI, -933 to -190;  = 0.003; replication: -612 bp; 95% CI, -870 to -354;  = 5.30 × 10). Variant status was significantly associated with transplant-free survival in both cohorts (discovery: age-, sex-, and ancestry-adjusted hazard ratio, 3.73; 95% CI, 1.92-7.28;  = 0.0001; replication: hazard ratio, 2.72; 95% CI, 1.26-5.88;  = 0.011). A substantial proportion of patients diagnosed with CHP have rare, protein-altering variants in telomere-related genes, which are associated with short peripheral blood telomere length and significantly reduced transplant-free survival.
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http://dx.doi.org/10.1164/rccm.201902-0360OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888660PMC
November 2019

A genome-wide association study of prostate cancer in Latinos.

Int J Cancer 2020 04 3;146(7):1819-1826. Epub 2019 Jul 3.

Department of Preventative Medicine, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA.

Latinos represent <1% of samples analyzed to date in genome-wide association studies of cancer. The clinical value of genetic information in guiding personalized medicine in populations of non-European ancestry will require additional discovery and risk locus characterization efforts across populations. In the present study, we performed a GWAS of prostate cancer (PrCa) in 2,820 Latino PrCa cases and 5,293 controls to search for novel PrCa risk loci and to examine the generalizability of known PrCa risk loci in Latino men. We also conducted a genetic admixture-mapping scan to identify PrCa risk alleles associated with local ancestry. Genome-wide significant associations were observed with 84 variants all located at the known PrCa risk regions at 8q24 (128.484-128.548) and 10q11.22 (MSMB gene). In admixture mapping, we observed genome-wide significant associations with local African ancestry at 8q24. Of the 162 established PrCa risk variants that are common in Latino men, 135 (83.3%) had effects that were directionally consistent as previously reported, among which 55 (34.0%) were statistically significant with p < 0.05. A polygenic risk model of the known PrCa risk variants showed that, compared to men with average risk (25th-75th percentile of the polygenic risk score distribution), men in the top 10% had a 3.19-fold (95% CI: 2.65, 3.84) increased PrCa risk. In conclusion, we found that the known PrCa risk variants can effectively stratify PrCa risk in Latino men. Larger studies in Latino populations will be required to discover and characterize genetic risk variants for PrCa and improve risk stratification for this population.
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http://dx.doi.org/10.1002/ijc.32525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028127PMC
April 2020

Telomere length and socioeconomic status at neighborhood and individual levels among 80,000 adults in the Genetic Epidemiology Research on Adult Health and Aging cohort.

Environ Epidemiol 2019 Jun 1;3(3):e049. Epub 2019 May 1.

Division of Research, Oakland, Kaiser Permanente Northern California, Oakland, California.

Background: Telomere length (TL) may serve as a biologic marker of aging. We examined neighborhood and individual-level socioeconomic status (SES) in relation to TL.

Methods: The study included 84,996 non-Hispanic white subjects from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, part of the Research Program on Genes, Environment and Health. Relative TL (T/S) was log transformed to improve normality and standardized to have mean 0 and variance 1. Neighborhood SES was measured using the Neighborhood Deprivation Index (NDI), and individual SES was measured by self-reported education level. We fit linear regression models of TL on age, sex, smoking, body mass index, comorbidities, NDI, and education level. We tested for differences in the associations by sex and nonlinearity in the association of NDI with TL.

Results: Each SD increase in NDI was associated with a decrease of 0.0192 in standardized TL, 95% confidence interval (CI) = -0.0306, -0.0078. There was no evidence of nonlinearity in the association of NDI with TL. We further found that less than high school education was associated with a decrease of 0.1371 in standardized TL, 95% CI = -0.1919, -0.0823 as compared to a college education. There were no differences in the associations by sex.

Conclusions: We found evidence that both lower neighborhood SES and lower individual-level SES are associated with shorter TL among non-Hispanic whites. Our findings suggest that socioeconomic factors may influence aging by contributing to shorter TL.
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http://dx.doi.org/10.1097/EE9.0000000000000049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939422PMC
June 2019
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