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

Authors

Lindsay Fernández-Rhodes, Department of Biobehavioral Health, Pennsylvania State University, 219 Biobehavioral Health Building, University Park, PA 16802, USA.
Mariaelisa Graff, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Victoria L. Buchanan, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Anne E. Justice, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Heather M. Highland, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Xiuqing Guo, The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502 USA.
Wanying Zhu, Vanderbilt Genetics Institute, Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Hung-Hsin Chen, Vanderbilt Genetics Institute, Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Kristin L. Young, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Kaustubh Adhikari, School of Mathematics and Statistics, Faculty of Science, Technology, Engineering and Mathematics, The Open University, MK7 6AA Milton Keynes, UK.
Nicholette D. Palmer, Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
Jennifer E. Below, Vanderbilt Genetics Institute, Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Jonathan Bradfield, Center for Applied Genomics, Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Alexandre C. Pereira, Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo, São Paulo 05508-220, Brazil.
LáShauntá Glover, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Daeeun Kim, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Adam G. Lilly, Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Poojan Shrestha, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Alvin G. Thomas, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Xinruo Zhang, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Minhui Chen, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Charleston W. Chiang, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Sara Pulit, Vertex Pharmaceuticals, W2 6BD Oxford, UK.
Andrea Horimoto, Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo, São Paulo 05508-220, Brazil.
Jose E. Krieger, Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo, São Paulo 05508-220, Brazil.
Marta Guindo-Martínez, The Charles Bronfman Institutes for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Michael Preuss, The Charles Bronfman Institutes for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Claudia Schumann, Hasso Plattner Institute, University of Potsdam, Digital Health Center, 14482 Potsdam, Germany.
Roelof A. Smit, The Charles Bronfman Institutes for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Gabriela Torres-Mejía, Department of Research in Cardiovascular Diseases, Diabetes Mellitus, and Cancer, Population Health Research Center, National Institute of Public Health, Cuernavaca, Morelos 62100, Mexico.
Victor Acuña-Alonzo, National Institute of Anthropology and History, Mexico City 06600, Mexico.
Gabriel Bedoya

Author Type(s)

Faculty

Journal Title

HGG Advances

First Page

100099

Document Type

Article

Publication Date

4-14-2022

Department

Medicine

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.

Recommended Citation

Fernández-Rhodes, L., Graff, M., Buchanan, V. L., Justice, A. E., Highland, H. M., Guo, X., Zhu, W., Chen, H., Young, K. L., Adhikari, K., Palmer, N. D., Below, J. E., Bradfield, J., Pereira, A. C., Glover, L., Kim, D., Lilly, A. G., Shrestha, P., Thomas, A. G., Zhang, X., Chen, M., Chiang, C. W., Pulit, S., Horimoto, A., Krieger, J. E., Guindo-Martínez, M., Preuss, M., Schumann, C., Smit, R. A., Torres-Mejía, G., Acuña-Alonzo, V., & Bedoya, G. (2022). Ancestral Diversity Improves Discovery and Fine-Mapping of Genetic Loci for Anthropometric Traits-The Hispanic/Latino Anthropometry Consortium. HGG Advances, 3 (2), 100099. https://doi.org/10.1016/j.xhgg.2022.100099