Genetic Diversity and Association Studies in US Hispanic/Latino Populations: Applications in the Hispanic Community Health Study/Study of Latinos
Open accessAbstract
US Hispanic/Latino individuals are diverse in genetic ancestry, culture, and environmental exposures. Here, we characterized and controlled for this diversity in genome-wide association studies (GWASs) for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We simultaneously estimated population-structure principal components (PCs) robust to familial relatedness and pairwise kinship coefficients (KCs) robust to population structure, admixture, and Hardy-Weinberg departures. The PCs revealed substantial genetic differentiation within and among six self-identified background groups (Cuban, Dominican, Puerto Rican, Mexican, and Central and South American). To control for variation among groups, we developed a multi-dimensional clustering method to define a "genetic-analysis group" variable that retains many properties of self-identified background while achieving substantially greater genetic homogeneity within groups and including participants with non-specific self-identification. In GWASs of 22 biomedical traits, we used a linear mixed model (LMM) including pairwise empirical KCs to account for familial relatedness, PCs for ancestry, and genetic-analysis groups for additional group-associated effects. Including the genetic-analysis group as a covariate accounted for significant trait variation in 8 of 22 traits, even after we fit 20 PCs. Additionally, genetic-analysis groups had significant heterogeneity of residual variance for 20 of 22 traits, and modeling this heteroscedasticity within the LMM reduced genomic inflation for 19 traits. Furthermore, fitting an LMM that utilized a genetic-analysis group rather than a self-identified background group achieved higher power to detect previously reported associations. We expect that the methods applied here will be useful in other studies with multiple ethnic groups, admixture, and relatedness.
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All statistical analyses were adjusted for sex and 3 genetic principal components estimated with the PC-air method, and linear mixed-model analyses were additionally covaried by a sparse genetic relationship matrix estimated with the PC-Relate method.
“All statistical analyses were adjusted for sex and 3 genetic principal components estimated with the PC-air method 29 implemented in GENESIS.Linear mixed-model analyses were additionally covaried by a sparse genetic relationship matrix estimated with the PC-Relate method 30 implemented in GENESIS.”
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Self-citation
- Authors
- Conomos, M. P., Laurie, C. A., Stilp, A. M., Gogarten, S. M., McHugh, C. P., Nelson, S. C., Sofer, T., Fernández-Rhodes, L., Justice, A. E., Graff, M., Young, K. L., Seyerle, A. A., Avery, C. L., Taylor, K. D., Rotter, J. I., Talavera, G. A., Daviglus, M. L., Wassertheil-Smoller, S., Schneiderman, N., Heiss, G., Kaplan, R. C., Franceschini, N., Reiner, A. P., Shaffer, J. R., Barr, R. G., Kerr, K. F., Browning, S. R., Browning, B. L., Weir, B. S., Avilés-Santa, M. L., Papanicolaou, G. J., Lumley, T., Szpiro, A. A., North, K. E., Rice, K., Thornton, T. A., & Laurie, C. C.
- Affiliations
- University of Washington (US)
- University of North Carolina at Chapel Hill (US)
- The Lundquist Institute (US)
- University of Illinois Chicago (US)
- University of Miami (US)
- Albert Einstein College of Medicine (US)
- University of Pittsburgh (US)
- Columbia University Irving Medical Center (US)
- National Institutes of Health (US)
- University of Auckland (NZ)
- Corresponding author
- Conomos, Matthew P.
- Laurie, Cathy C.
- ORCID
- Conomos, Matthew P.
- Laurie, Cecelia A.
- Stilp, Adrienne M.
- Gogarten, Stephanie M.
- McHugh, Caitlin P.
- Nelson, Sarah C.
- Sofer, Tamar
- Justice, Anne E.
- Graff, Mariaelisa
- Young, Kristin L.
- Seyerle, Amanda A.
- Rotter, Jerome I.
- Daviglus, Martha L.
- Heiss, Gerardo
- Kaplan, Robert C.
- Franceschini, Nora
- Reiner, Alex P.
- Shaffer, John R.
- Barr, R. Graham
- Kerr, Kathleen F.
- Browning, Sharon R.
- Browning, Brian L.
- Weir, Bruce S.
- Papanicolaou, George J.
- Szpiro, Adam A.
- North, Kari E.
- Thornton, Timothy A.
- Laurie, Cathy C.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 98
- Issue
- 1
- Pages
- 165-184
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC4716704
- OpenAlex
- W2226732401
- Cited by
- 336
- References
- 13
- Citations by year
- 2026: 31 · 2025: 30 · 2024: 24 · 2023: 40 · 2022: 37 · 2021: 39 · 2020: 20 · 2019: 36 · 2018: 30 · 2017: 30 · 2016: 18 · 2015: 1
- FWCI
- 25.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- UNC Libraries
- Funders
- U.S. Department of Health and Human Services
- Office of Dietary Supplements (N01-HC65237, N01-HC65235, N01-HC65233, N01-HC65234, N01-HC65236)
- University of Miami (N01-HC65236, N01-HC65237, N01- HC65235, N01- HC65234, N01-HC65233)
- Northwestern University (N01‐HC65236, N01HC65237, N01-HC65233, N01-HC65235, N01-HC65234)
- San Diego State University (N01-HC65233, N01-HC65234, N01-HC65235, N01-HC65236, N01‐HC‐65237)
- University of Washington (HHSN268201300005C)
- National Institutes of Health (n01hc65235-13-0-1, n01hc65234-5-0-0, UL1TR000124, n01hc65237-14-0-1, n01hc65236-16-0-1, N01-HC65236, N01-HC65235, N01-HC65234, N01-HC65237, n01hc065233-1-0-0, DK-063491)
- National Heart, Lung, and Blood Institute (DK-063491, N01HC65235, (N01-HC-65237, N01‐HC‐65234, N01 HC065235, HHSN268201300005C, N01-HC65236, N01 HC065237, N01‐HC65233, N01 HC065234, N01 HC065236, HHSN268201300005C AM03, N01 HC065233)
- National Institute on Deafness and Other Communication Disorders (N01-HC65234, N01-HC65235, N01-HC65233, N01-HC65237, N01-HC65236)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, N01-HC65234, N01-HC65236, N01-HC65233, N01-HC65235, N01-HC65237, R01DK101855, P30DK063491)
- National Institute of Dental and Craniofacial Research (MOD03, N01-HC65236, N01-HC65234, N01-HC65237, HHSN268201300005C, HHSN268201300005C AM03, N01-HC65235, N01-HC65233, 13GRNT16490017)
- National Center for Advancing Translational Sciences
- National Institute on Minority Health and Health Disparities (N01-HC65233, N01-HC65234, N01-HC65235, N01-HC65237, N01-HC65236)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Race, Genetics, and Society
- Keywords
- Hispanic/Latino populations, genetic ancestry, admixture, population structure, kinship coefficient, linear mixed models, genomic inflation, heteroscedasticity, genetic diversity, genome-wide association study, Hispanic Community Health Study/Study of Latinos, relatedness
- MeSH terms
- Hispanic or Latino, Humans, United States, Genetic Variation, Genome-Wide Association Study
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