Ancestral Diversity Improves Discovery and Fine-Mapping of Genetic Loci for Anthropometric Traits-the Hispanic/Latino Anthropometry Consortium

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Citation

Fernández-Rhodes, Lindsay; Graff, Mariaelisa; Buchanan, Victoria L.; Justice, Anne E.; Highland, Heather M.; Guo, Xiuqing; Zhu, Wanying; Chen, Hung-Hsin; Young, Kristin L.; & Adhikari, Kaustubh, et al. (2022). Ancestral Diversity Improves Discovery and Fine-Mapping of Genetic Loci for Anthropometric Traits-the Hispanic/Latino Anthropometry Consortium. HGG Advances, 3(2), 100099. PMCID: PMC8990175

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.

URL

http://dx.doi.org/10.1016/j.xhgg.2022.100099

Reference Type

Journal Article

Year Published

2022

Journal Title

HGG Advances

Author(s)

Fernández-Rhodes, Lindsay
Graff, Mariaelisa
Buchanan, Victoria L.
Justice, Anne E.
Highland, Heather M.
Guo, Xiuqing
Zhu, Wanying
Chen, Hung-Hsin
Young, Kristin L.
Adhikari, Kaustubh
Palmer, Nicholette D.
Below, Jennifer E.
Bradfield, Jonathan P.
Pereira, Alexandre C.
Glover, LáShauntá
Kim, Daeeun
Lilly, Adam G.
Shrestha, Poojan
Thomas, Alvin G.
Zhang, Xinruo
Chen, Minhui
Chiang, Charleston W. K.
Pulit, Sara
Horimoto, Andrea
Krieger, Jose E.
Guindo-Martínez, Marta
Preuss, Michael
Schumann, Claudia
Smit, Roelof A. J.
Torres-Mejía, Gabriela
Acuña-Alonzo, Victor
Bedoya, Gabriel
Bortolini, Maria-Cátira
Canizales-Quinteros, Samuel
Gallo, Carla
González-José, Rolando
Poletti, Giovanni
Rothhammer, Francisco
Hakonarson, Hakon
Igo, Robert
Adler, Sharon G.
Iyengar, Sudha K.
Nicholas, Susanne B.
Gogarten, Stephanie M.
Isasi, Carmen R.
Papnicolaou, George
Stilp, Adrienne M.
Qi, Qibin
Kho, Minjung
Smith, Jennifer A.
Langefeld, Carl D.
Wagenknecht, Lynne
Mckean-Cowdin, Roberta
Gao, Xiaoyi Raymond
Nousome, Darryl
Conti, David V.
Feng, Ye
Allison, Matthew A.
Arzumanyan, Zorayr
Buchanan, Thomas A.
Ida Chen, Yii-Der
Genter, Pauline M.
Goodarzi, Mark O.
Hai, Yang
Hsueh, Willa
Ipp, Eli
Kandeel, Fouad R
Lam, Kelvin
Li, Xiaohui
Nadler, Jerry L.
Raffel, Leslie J.
Roll, Kathryn
Sandow, Kevin
Tan, Jingyi
Taylor, Kent D.
Xiang, Anny H.
Yao, Jie
Audirac-Chalifour, Astride
de Jesus Peralta Romero, Jose
Hartwig, Fernando P.
Horta, Bernando
Blangero, John
Curran, Joanne E.
Duggirala, Ravindranath
Lehman, Donna E.
Puppala, Sobha
Fejerman, Laura
John, Esther M.
Aguilar-Salinas, Carlos A.
Burtt, Noël P.
Florez, Jose C.
García-Ortíz, Humberto
González-Villalpando, Clicerio
Mercader, Joseph
Orozco, Lorena
Tusié-Luna, Teresa
Blanco, Estela
Gahagan, Sheila
Cox, Nancy J.
Hanis, Craig
Butte, Nancy F.
Cole, Shelley A.
Comuzzie, Anthony G.
Voruganti, Saroja
Rohde, Rebecca
Wang, Yujie
Sofer, Tamar
Ziv, Elad
Grant, Struan F. A.
Ruiz-Linares, Andres
Rotter, Jerome I.
Haiman, Christopher A.
Parra, Esteban J.
Cruz, Miguel
Loos, Ruth J. F.
North, Kari E.

Article Type

Regular

PMCID

PMC8990175

Data Set/Study

Hispanic/Latino Anthropometry (HISLA) Consortium

Race/Ethnicity

Hispanic

ORCiD

Lilly - 0000-0002-3740-1540
Graff - 0000-0001-6380-1735
Highland - 000-0002-3583-8239