Dataset Information

Analyses of biomarker traits in diverse UK biobank participants identify associations missed by European-centric analysis strategies.

ABSTRACT: Despite the dramatic underrepresentation of non-European populations in human genetics studies, researchers continue to exclude participants of non-European ancestry, as well as variants rare in European populations, even when these data are available. This practice perpetuates existing research disparities and can lead to important and large effect size associations being missed. Here, we conducted genome-wide association studies (GWAS) of 31 serum and urine biomarker quantitative traits in African (n = 9354), East Asian (n = 2559), and South Asian (n = 9823) ancestry UK Biobank (UKBB) participants. We adjusted for all known GWAS catalog variants for each trait, as well as novel signals identified in a recent European ancestry-focused analysis of UKBB participants. We identify 7 novel signals in African ancestry and 2 novel signals in South Asian ancestry participants (p < 1.61E-10). Many of these signals are highly plausible, including a cis pQTL for the gene encoding gamma-glutamyl transferase and PIEZO1 and G6PD variants with impacts on HbA1c through likely erythrocytic mechanisms. This work illustrates the importance of using the genetic data we already have in diverse populations, with novel discoveries possible in even modest sample sizes.

SUBMITTER: Sun Q

PROVIDER: S-EPMC8792153 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analyses of biomarker traits in diverse UK biobank participants identify associations missed by European-centric analysis strategies.

Sun Quan Q Graff Misa M Rowland Bryce B Wen Jia J Huang Le L Miller-Fleming Tyne W TW Haessler Jeffrey J Preuss Michael H MH Chai Jin-Fang JF Lee Moa P MP Avery Christy L CL Cheng Ching-Yu CY Franceschini Nora N Sim Xueling X Cox Nancy J NJ Kooperberg Charles C North Kari E KE Li Yun Y Raffield Laura M LM

Journal of human genetics 20210811 2

Despite the dramatic underrepresentation of non-European populations in human genetics studies, researchers continue to exclude participants of non-European ancestry, as well as variants rare in European populations, even when these data are available. This practice perpetuates existing research disparities and can lead to important and large effect size associations being missed. Here, we conducted genome-wide association studies (GWAS) of 31 serum and urine biomarker quantitative traits in Afr ...[more]

PMID: 34376796

Similar Datasets

Project description:ImportanceCalcium channel blocker (CCB) use has been associated with an increased risk of glaucoma in exploratory studies.ObjectiveTo examine the association of systemic CCB use with glaucoma and related traits among UK Biobank participants.Design, setting, and participantsThis population-based cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis of glaucoma status, intraocular pressure (IOP), and optical coherence tomography (OCT)-derived inner retinal layer thicknesses. Data analysis was conducted in January 2023.ExposureCalcium channel blocker use was assessed in a baseline touchscreen questionnaire and confirmed during an interview led by a trained nurse.Main outcomes and measuresThe primary outcome measures included glaucoma status, corneal-compensated IOP, and 2 OCT-derived inner retinal thickness parameters (macular retinal nerve fiber layer [mRNFL] and macular ganglion cell-inner plexiform layer [mGCIPL] thicknesses). We performed logistic regression and linear regression analyses to test for associations with glaucoma status and IOP and OCT-derived inner retinal thickness parameters, respectively.ResultsThis study included 427 480 adults. Their median age was 58 (IQR, 50-63) years, and more than half (54.1%) were women. There were 33 175 CCB users (7.8%). Participants who had complete data for glaucoma status (n = 427 480), IOP (n = 97 100), and OCT-derived inner retinal layer thicknesses (n = 41 023) were eligible for respective analyses. After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, use of CCBs (but not other antihypertensive agents) was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001). Calcium channel blocker use was also associated with thinner mGCIPL (-0.34 μm [95% CI, -0.54 to -0.15 μm]; P = .001) and mRNFL (-0.16 μm [95% CI, -0.30 to -0.02 μm]; P = .03) thicknesses but not IOP (-0.01 mm Hg [95% CI, -0.09 to 0.07 mm Hg]; P = .84).Conclusions and relevanceIn this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39% higher odds of glaucoma. Calcium channel blocker use was also associated with thinner mGCIPL and mRNFL thicknesses, providing a structural basis that supports the association with glaucoma. The lack of association of CCB use with IOP suggests that an IOP-independent mechanism of glaucomatous neurodegeneration may be involved. Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.

Dataset Information

Analyses of biomarker traits in diverse UK biobank participants identify associations missed by European-centric analysis strategies.

Publications

Analyses of biomarker traits in diverse UK biobank participants identify associations missed by European-centric analysis strategies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets