Population structure and admixture are key confounders in genome-wide association and medical resequencing studies. In particular, accounting for difference in ancestry among cases and controls, both in terms of genomic and geographic location, is critical for proper analysis and interpretation of studies with multi- and trans-ethnic samples. Genomic studies of Hispanics/Latinos, the largest and fastest growing minority group in the US, reveal that they are a highly genetically heterogeneous admixed group with immense variation among individuals and populations in the proportions of African, European, and Native American ancestry. Furthermore, while Mexican populations have been characterized genomically to some extent, genetic studies of populations from the Caribbean and South America have been largely underrepresented. Knowledge of the underlying complex genetic structure of US Hispanic/Latino and Caribbean populations is, therefore, essential to ensuring robustness of genotype-phenotype associations and understanding the medical relevance of associated variants across diverse populations in the US and throughout the Americas. Furthermore, since much is known about the African and European migrations into the Americas over the past 500 years, population genetic studies of Hispanics/Latinos serve as an excellent model for developing novel algorithms and approaches for characterizing fine-scale genetic structure of admixed populations, in general. This project will extend current studies of population genetic structure in US Hispanics/Latinos by densely genotyping 180 parent-offspring triads and sequencing the genomes of 30 triads from six U.S. populations of Caribbean- descent: Puerto Rico, Cuba, Dominican Republic, Haiti, Honduras and Colombia. We will combine the SNP, CNV, and whole genome sequence (WGS) data with other publically available genomic resources including the International HapMap project and the 1000 Genomes project to understand the complex genetic architecture of Hispanic/Latino populations in the US. We will accomplish this goal through the following specific aims: 1) Generate dense SNP genotype data across our sample of 180 triads using the Affymetrix 6.0 whole genome SNP chip (~1 million SNPs and CNVs), 2) Generate high coverage WGS data and build the complete genomes of 30 triads (5 from each of 6 populations) to at least 20X coverage, 3) Characterize population structure and admixture in our US Hispanic/Latino triads based on SNP genotype and WGS data including comparison to HapMap and 1000G data, and Aim 4) Assess and account for the impact of substructure on disease-association tests in order to improve the next generation of trans and multi-ethnic medical genomic studies. Our project is highly significant because it will provide immediate insights and new statistical methods to improve study design and genetic analysis for medical genomic studies in Hispanics/Latinos, other complex admixed groups, and multi- and trans-ethnic studies.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-GGG-F (02))
Program Officer
Krasnewich, Donna M
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University of Miami School of Medicine
Schools of Medicine
Coral Gables
United States
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Page, Joshua; Constantino, John Nicholas; Zambrana, Katherine et al. (2016) Quantitative autistic trait measurements index background genetic risk for ASD in Hispanic families. Mol Autism 7:39
Poznik, G David; Xue, Yali; Mendez, Fernando L et al. (2016) Punctuated bursts in human male demography inferred from 1,244 worldwide Y-chromosome sequences. Nat Genet 48:593-9
Homburger, Julian R; Moreno-Estrada, Andrés; Gignoux, Christopher R et al. (2015) Genomic Insights into the Ancestry and Demographic History of South America. PLoS Genet 11:e1005602
Moreno-Estrada, Andrés; Gignoux, Christopher R; Fernández-López, Juan Carlos et al. (2014) Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science 344:1280-5
Chung, Ren-Hua; Tsai, Wei-Yun; Martin, Eden R (2014) Family-based association test using both common and rare variants and accounting for directions of effects for sequencing data. PLoS One 9:e107800
Corona, Erik; Chen, Rong; Sikora, Martin et al. (2013) Analysis of the genetic basis of disease in the context of worldwide human relationships and migration. PLoS Genet 9:e1003447
Botigué, Laura R; Henn, Brenna M; Gravel, Simon et al. (2013) Gene flow from North Africa contributes to differential human genetic diversity in southern Europe. Proc Natl Acad Sci U S A 110:11791-6
Gravel, Simon; Zakharia, Fouad; Moreno-Estrada, Andres et al. (2013) Reconstructing Native American migrations from whole-genome and whole-exome data. PLoS Genet 9:e1004023
Moreno-Estrada, Andres; Gravel, Simon; Zakharia, Fouad et al. (2013) Reconstructing the population genetic history of the Caribbean. PLoS Genet 9:e1003925
Gravel, Simon (2012) Population genetics models of local ancestry. Genetics 191:607-19

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