Analyses of Biomarker Traits in Diverse UK Biobank Participants Identify Associations Missed by European-Centric Analysis Strategies

Citation

Sun, Quan; Graff, Mariaelisa; Rowland, Bryce; Wen, Jia; Huang, Le; Miller-Fleming, Tyne W.; Haessler, Jeffrey; Preuss, Michael H.; Chai, Jin Fang; & Lee, Moa P., et al. (2022). Analyses of Biomarker Traits in Diverse UK Biobank Participants Identify Associations Missed by European-Centric Analysis Strategies. Journal of Human Genetics, 67(2), 87-93. PMCID: PMC8792153

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.

URL

http://dx.doi.org/10.1038/s10038-021-00968-0

Reference Type

Journal Article

Year Published

2022

Journal Title

Journal of Human Genetics

Author(s)

Sun, Quan
Graff, Mariaelisa
Rowland, Bryce
Wen, Jia
Huang, Le
Miller-Fleming, Tyne W.
Haessler, Jeffrey
Preuss, Michael H.
Chai, Jin Fang
Lee, Moa P.
Avery, Christy L.
Cheng, Ching-Yu
Franceschini, Nora
Sim, Xueling
Cox, Nancy J.
Kooperberg, Charles L.
North, Kari E.
Li, Yun
Raffield, Laura M.

Article Type

Regular

PMCID

PMC8792153

Data Set/Study

UK Biobank Study

Race/Ethnicity

African Ancestry
East Asian Ancestry
South Asian Ancestry

ORCiD

Avery - 0000-0002-1044-8162
Graff - 0000-0001-6380-1735