Dataset Information

Genetic Loci Associated With COVID-19 Positivity and Hospitalization in White, Black, and Hispanic Veterans of the VA Million Veteran Program.

ABSTRACT: SARS-CoV-2 has caused symptomatic COVID-19 and widespread death across the globe. We sought to determine genetic variants contributing to COVID-19 susceptibility and hospitalization in a large biobank linked to a national United States health system. We identified 19,168 (3.7%) lab-confirmed COVID-19 cases among Million Veteran Program participants between March 1, 2020, and February 2, 2021, including 11,778 Whites, 4,893 Blacks, and 2,497 Hispanics. A multi-population genome-wide association study (GWAS) for COVID-19 outcomes identified four independent genetic variants (rs8176719, rs73062389, rs60870724, and rs73910904) contributing to COVID-19 positivity, including one novel locus found exclusively among Hispanics. We replicated eight of nine previously reported genetic associations at an alpha of 0.05 in at least one population-specific or the multi-population meta-analysis for one of the four MVP COVID-19 outcomes. We used rs8176719 and three additional variants to accurately infer ABO blood types. We found that A, AB, and B blood types were associated with testing positive for COVID-19 compared with O blood type with the highest risk for the A blood group. We did not observe any genome-wide significant associations for COVID-19 severity outcomes among those testing positive. Our study replicates prior GWAS findings associated with testing positive for COVID-19 among mostly White samples and extends findings at three loci to Black and Hispanic individuals. We also report a new locus among Hispanics requiring further investigation. These findings may aid in the identification of novel therapeutic agents to decrease the morbidity and mortality of COVID-19 across all major ancestral populations.

SUBMITTER: Peloso GM

PROVIDER: S-EPMC8864634 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Genetic Loci Associated With COVID-19 Positivity and Hospitalization in White, Black, and Hispanic Veterans of the VA Million Veteran Program.

Peloso Gina M GM Tcheandjieu Catherine C McGeary John E JE Posner Daniel C DC Ho Yuk-Lam YL Zhou Jin J JJ Hilliard Austin T AT Joseph Jacob J O'Donnell Christopher J CJ Efird Jimmy T JT Crawford Dana C DC Wu Wen-Chih WC Arjomandi Mehrdad M Sun Yan V YV Assimes Themistocles L TL Huffman Jennifer E JE

Frontiers in genetics 20220203

SARS-CoV-2 has caused symptomatic COVID-19 and widespread death across the globe. We sought to determine genetic variants contributing to COVID-19 susceptibility and hospitalization in a large biobank linked to a national United States health system. We identified 19,168 (3.7%) lab-confirmed COVID-19 cases among Million Veteran Program participants between March 1, 2020, and February 2, 2021, including 11,778 Whites, 4,893 Blacks, and 2,497 Hispanics. A multi-population genome-wide association s ...[more]

PMID: 35222515

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Project description:Background and objectivesNearly all genetic analyses of Parkinson disease (PD) have been in populations of European ancestry. We sought to test the ability of a machine learning method to extract accurate PD diagnoses from an electronic medical record (EMR) system, to see whether genetic variants identified in European populations generalize to individuals of African and Hispanic ancestries, and to compare the rates of PD across ancestries.MethodsA machine learning method using natural language processing was applied to EMRs of US veterans participating in the VA Million Veteran Program (MVP) to identify individuals with PD. These putative cases were vetted via blind chart review by a movement disorder specialist. A polygenic risk score (PRS) of 90 established genetic variants whose genotypes were imputed from a customized Axiom Biobank Array was evaluated in different case groups.ResultsThe EMR prediction scores had a distinct trimodal distribution, with 97% of the high group and only 30% of the middle group having a credible diagnosis of PD. Using the 3,542 cases from the high group matched 4:1 to controls, the PRS was highly predictive in individuals of European ancestry (n = 3,137 cases; OR = 1.82; p = 8.01E-48), and nearly identical effect sizes were seen in individuals of African (n = 184; OR = 2.07; p = 3.4E-4) and Hispanic ancestries (n = 221; OR = 2.13; p = 3.9E-6). The PRS was much less predictive for the 2,757 European ancestry cases who had an ICD code for PD but for whom the machine learning method had a lower confidence in their diagnosis. No novel ancestry-specific genetic variants were identified. Individuals with African ancestry had one-quarter the rate of PD compared with European or Hispanic ancestries aged 60-70 years and one half the rate in the 70-80 years age range. African American cases had a higher proportion of their DNA originating in Europe compared with African American controls.DiscussionMachine learning can reliably classify PD using data from a large EMR. Larger studies of non-European populations are required to confirm the generalizability of PD risk variants identified in populations of European ancestry and the increased risk coming from a higher proportion of European DNA in African Americans.

Project description:BackgroundVeterans of the 1990-1991 Gulf War have experienced excess health problems, most prominently the multisymptom condition Gulf War illness (GWI). The Department of Veterans Affairs (VA) Cooperative Studies Program #2006 "Genomics of Gulf War Illness in Veterans" project was established to address important questions concerning pathobiological and genetic aspects of GWI. The current study evaluated patterns of chronic ill health/GWI in the VA Million Veteran Program (MVP) Gulf War veteran cohort in relation to wartime exposures and key features of deployment, 27-30 years after Gulf War service.MethodsMVP participants who served in the 1990-1991 Gulf War completed the MVP Gulf War Era Survey in 2018-2020. Survey responses provided detailed information on veterans' health, Gulf War exposures, and deployment time periods and locations. Analyses determined associations of three defined GWI/ill health outcomes with Gulf War deployment characteristics and exposures.ResultsThe final cohort included 14,103 veterans; demographic and military characteristics of the sample were similar to the full population of U.S. 1990-1991 Gulf War veterans. Overall, a substantial number of veterans experienced chronic ill health, as indicated by three defined outcomes: 49% reported their health as fair or poor, 31% met Centers for Disease Control and Prevention criteria for severe GWI, and 20% had been diagnosed with GWI by a healthcare provider. Health outcomes varied consistently with veterans' demographic and military characteristics, and with exposures during deployment. All outcomes were most prevalent among youngest veterans (< 50 years), Army and Marine Corps veterans, enlisted personnel (vs. officers), veterans located in Iraq and/or Kuwait for at least 7 days, and veterans who remained in theater from January/February 1991 through the summer of 1991. In multivariable models, GWI/ill health was most strongly associated with three exposures: chemical/biological warfare agents, taking pyridostigmine bromide pills, and use of skin pesticides.ConclusionsResults from this large cohort indicate that GWI/chronic ill health continues to affect a large proportion of Gulf War veterans in patterns associated with 1990-1991 Gulf War deployment and exposures. Findings establish a foundation for comprehensive evaluation of genetic factors and deployment exposures in relation to GWI risk and pathobiology.

Project description:AbstractU.S. Veterans Affairs (VA) patients' multi-system use can create challenges for VA clinicians who are responsible for coordinating Veterans' use of non-VA care, including VA-purchased care ("Community Care") and Medicare.To examine the relationship between drive distance and time-key eligibility criteria for Community Care-and VA reliance (proportion of care received in VA versus Medicare and Community Care) among Veterans at high risk for hospitalization. We used prepolicy data to anticipate the impact of the 2014 Choice Act and 2018 Maintaining Internal Systems and Strengthening Integrated Outside Networks Act (MISSION Act), which expanded access to Community Care.Cross-sectional analysis using fractional logistic regressions to examine the relationship between a Veteran's reliance on VA for outpatient primary, mental health, and other specialty care and their drive distance/time to a VA facility.Thirteen thousand seven hundred three Veterans over the age of 65 years enrolled in VA and fee-for-service Medicare in federal fiscal year 2014 who were in the top 10th percentile for hospitalization risk.Key explanatory variables were patients' drive distance to VA > 40 miles (Choice Act criteria) and drive time to VA ≥ 30 minutes for primary and mental health care and ≥60 minutes for specialty care (MISSION Act criteria).Veterans at high risk for hospitalization with drive distance eligibility had increased odds of an outpatient specialty care visit taking place in VA when compared to Veterans who did not meet Choice Act eligibility criteria (odds ratio = 1.10, 95% confidence interval 1.05-1.15). However, drive time eligibility (MISSION Act criteria) was associated with significantly lower odds of an outpatient specialty care visit taking place in VA (odds ratio = 0.69, 95% confidence interval 0.67, 0.71). Neither drive distance nor drive time were associated with reliance for outpatient primary care or mental health care.VA patients who are at high risk for hospitalization may continue to rely on VA for outpatient primary care and mental health care despite access to outside services, but may increase use of outpatient specialty care in the community in the MISSION era, increasing demand for multi-system care coordination.

Project description:ImportanceBlack men have higher prostate cancer incidence and mortality than non-Hispanic White men. However, Black men have been underrepresented in clinical trials of prostate-specific antigen (PSA) screening; thus, there is a lack of data to guide screening recommendations for this population.ObjectiveTo assess whether PSA screening is associated with reduced risk of prostate cancer-specific mortality (PCSM) among non-Hispanic Black men.Design, setting, and participantsThis retrospective cohort study used data from the US Veterans Health Administration Informatics and Computing Infrastructure for men aged 55 to 69 years who self-identified as non-Hispanic Black or non-Hispanic White and were diagnosed with intermediate-, high-, or very high-risk prostate cancer from January 1, 2004, to December 31, 2017. Data were analyzed from August 2021 to March 2022.ExposuresProstate-specific antigen screening rate, defined as the percentage of years in which PSA screening was conducted during the 5 years before diagnosis of prostate cancer.Main outcomes and measuresThe primary outcome was risk of PCSM among Black men and White men. The association between PSA screening and risk of PCSM was assessed using Fine-Gray regression analysis. Risk of PCSM was also assessed categorically among patients classified as having no prior PSA screening, some screening (less than annual), or annual screening in the 5 years before diagnosis.ResultsThe study included 45 834 veterans (mean [SD] age, 62.7 [3.8] years), of whom 14 310 (31%) were non-Hispanic Black men and 31 524 (69%) were non-Hispanic White men. The PSA screening rate was associated with a lower risk of PCSM among Black men (subdistribution hazard ratio [sHR], 0.56; 95% CI, 0.41-0.76; P = .001) and White men (sHR, 0.58; 95% CI, 0.46-0.75; P = .001). On subset analysis, annual screening (vs some screening) was associated with a significant reduction in risk of PCSM among Black men (sHR, 0.65; 95% CI, 0.46-0.92; P = .02) but not among White men (sHR, 0.91; 95% CI, 0.74-1.11; P = .35).Conclusions and relevanceIn this cohort study, PSA screening was associated with reduced risk of PCSM among non-Hispanic Black men and non-Hispanic White men. Annual screening was associated with reduced risk of PCSM among Black men but not among White men, suggesting that annual screening may be particularly important for Black men. Further research is needed to identify appropriate populations and protocols to maximize the benefits of PSA screening.

Project description:BackgroundGenetic studies may help identify causal pathways; therefore, we sought to identify genetic determinants of ideal CVH and their association with CVD outcomes in the multi-population Veteran Administration Million Veteran Program.MethodsAn ideal health score (IHS) was calculated from 3 clinical factors (blood pressure, total cholesterol, and blood glucose levels) and 3 behavioral factors (smoking status, physical activity, and BMI), ascertained at baseline. Multi-population genome-wide association study (GWAS) was performed on IHS and binary ideal health using linear and logistic regression, respectively. Using the genome-wide significant SNPs from the IHS GWAS, we created a weighted IHS polygenic risk score (PRSIHS) which was used (i) to conduct a phenome-wide association study (PheWAS) of associations between PRSIHS and ICD-9 phenotypes and (ii) to further test for associations with mortality and selected CVD outcomes using logistic and Cox regression and, as an instrumental variable, in Mendelian Randomization.ResultsThe discovery and replication cohorts consisted of 142,404 (119,129 European American (EUR); 16,495 African American (AFR)), and 45,766 (37,646 EUR; 5,366 AFR) participants, respectively. The mean age was 65.8 years (SD = 11.2) and 92.7% were male. Overall, 4.2% exhibited ideal CVH based on the clinical and behavioral factors. In the multi-population meta-analysis, variants at 17 loci were associated with IHS and each had known GWAS associations with multiple components of the IHS. PheWAS analysis in 456,026 participants showed that increased PRSIHS was associated with a lower odds ratio for many CVD outcomes and risk factors. Both IHS and PRSIHS measures of ideal CVH were associated with significantly less CVD outcomes and CVD mortality.ConclusionA set of high interest genetic variants contribute to the presence of ideal CVH in a multi-ethnic cohort of US Veterans. Genetically influenced ideal CVH is associated with lower odds of CVD outcomes and mortality.

Dataset Information

Genetic Loci Associated With COVID-19 Positivity and Hospitalization in White, Black, and Hispanic Veterans of the VA Million Veteran Program.

Publications

Genetic Loci Associated With COVID-19 Positivity and Hospitalization in White, Black, and Hispanic Veterans of the VA Million Veteran Program.

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