Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium

Lindsay Fernández-Rhodes, Mariaelisa Graff, Victoria L. Buchanan, Anne E. Justice, Heather M. Highland, Xiuqing Guo, Wanying Zhu, Hung Hsin Chen, Kristin L. Young, Kaustubh Adhikari, Nicholette D. Palmer, Jennifer E. Below, Jonathan Bradfield, Alexandre C. Pereira, LáShauntá S. Glover, Daeeun Kim, Adam G. Lilly, Poojan Shrestha, Alvin G. Thomas, Xinruo ZhangMinhui Chen, Charleston W.K. Chiang, Sara Pulit, Andrea Horimoto, Jose E. Krieger, Marta Guindo-Martínez, Michael Preuss, Claudia Schumann, Roelof A.J. Smit, Gabriela Torres-Mejía, Victor Acuña-Alonzo, Gabriel Bedoya, Maria Cátira Bortolini, Samuel Canizales-Quinteros, Carla Gallo, Rolando González-José, Giovanni Poletti, Francisco Rothhammer, Hakon Hakonarson, Robert Igo, Sharon G. Adler, Sudha K. Iyengar, Susanne B. Nicholas, Stephanie M. Gogarten, Carmen R. Isasi, George Papnicolaou, Adrienne M. Stilp, Qibin Qi, Minjung Kho, Jennifer A. Smith

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish (US)
Article number100099
JournalHuman Genetics and Genomics Advances
Issue number2
StatePublished - Apr 14 2022

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics(clinical)


Dive into the research topics of 'Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium'. Together they form a unique fingerprint.

Cite this