Faculty, Staff and Student Publications
Language
English
Publication Date
4-14-2022
Journal
Human Genetics and Genomics Advances
DOI
10.1016/j.xhgg.2022.100099
PMID
35399580
PMCID
PMC8990175
PubMedCentral® Posted Date
3-11-2022
PubMedCentral® Full Text Version
Post-print
Abstract
Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.
Keywords
Hispanic/Latino, anthropometrics, obesity, diversity, trans-ancestral or trans-ethnic, fine-mapping, population stratification
Published Open-Access
yes
Recommended Citation
Fernández-Rhodes, Lindsay; Graff, Mariaelisa; Buchanan, Victoria L; et al., "Ancestral Diversity Improves Discovery and Fine-Mapping of Genetic Loci for Anthropometric Traits–The Hispanic/Latino Anthropometry Consortium" (2022). Faculty, Staff and Student Publications. 757.
https://digitalcommons.library.tmc.edu/uthsph_docs/757
Included in
Genetic Phenomena Commons, Genetic Processes Commons, Medical Genetics Commons, Public Health Commons
Comments
This article has been corrected. See HGG Adv. 2022 Oct 11;4(1):100149.