The Phenotypic Consequences of Genetic Divergence between Admixed Latin American Populations: Antioquia and Chocó, Colombia

Abstract

Genome-wide association studies have uncovered thousands of genetic variants that are associated with a wide variety of human traits. Knowledge of how trait-associated variants are distributed within and between populations can provide insight into the genetic basis of group-specific phenotypic differences, particularly for health-related traits. We analyzed the genetic divergence levels for (i) individual trait-associated variants and (ii) collections of variants that function together to encode polygenic traits, between two neighboring populations in Colombia that have distinct demographic profiles: Antioquia (Mestizo) and Chocó (Afro-Colombian). Genetic ancestry analysis showed 62% European, 32% Native American, and 6% African ancestry for Antioquia compared to 76% African, 10% European, and 14% Native American ancestry for Chocó, consistent with demography and previous results. Ancestry differences can confound cross-population comparison of polygenic risk scores (PRS); however, we did not find any systematic bias in PRS distributions for the two populations studied here, and population-specific differences in PRS were, for the most part, small and symmetrically distributed around zero. Both genetic differentiation at individual trait-associated SNPs and population-specific PRS differences between Antioquia and Chocó largely reflected anthropometric phenotypic differences that can be readily observed between the populations along with reported disease prevalence differences. Cases where population-specific differences in genetic risk did not align with observed trait (disease) prevalence point to the importance of environmental contributions to phenotypic variance, for both infectious and complex, common disease. The results reported here are distributed via a web-based platform for searching trait-associated variants and PRS divergence levels at http://map.chocogen.com.

The Impact of Ethnicity and Genetic Ancestry on Disease Prevalence and Risk in Colombia

“…Latin American populations are highly diverse and characterized by distinct combinations of African, European, and Native American ancestry (Bryc et al, 2010;Ruiz-Linares et al, 2014;Homburger et al, 2015;Norris et al, 2018Norris et al, , 2020. In addition, as we have shown here, Colombia itself is an ethnically diverse country with distinct ancestry profiles for different regions in the country (Rojas Morales et al, 2007;Rishishwar et al, 2015b;Conley et al, 2017;Nagar et al, 2019;Chande et al, 2020a). Thus, the connections between ancestry and health outcomes reported here may or may not apply to other countries or even to different populations sampled within Colombia.…”

“…Variant identifiers (rsid), effect alleles, effect sizes, and p -values were collected from for each selected trait-study combination. Curated variant lists for each trait were subjected to LD clumping (“--clump-r2 0.2”) and used to calculate PRS for imputed genomic variant data for the UniCES Medellín cohort using PLINK (v1.90b6.16), as previously reported ( Chande et al, 2018 , 2020a ). PRS for each condition or disease i were calculated as the sum of the effect alleles across all trait-associated SNPs as – – where corresponds to homozygous absent, heterozygous present, or homozygous present effect alleles at each variant, and corresponds to the total number of alleles with base calls at each variant.…”

“…Colombian genomic diversity represents a rich and largely untapped resource that can be used to support the development of genomic medicine locally in Colombia and around the world. We have been working to build local capacity in precision medicine via population and clinical genomic studies of diverse Colombian populations over the last decade ( Rishishwar et al, 2015a , b ; Jordan, 2016 ; Medina-Rivas et al, 2016 ; Chande et al, 2017 , 2020a , b ; Conley et al, 2017 ; Norris et al, 2018 , 2020 ; Nagar et al, 2019 ). These studies share the broad aims of (1) characterizing patterns of genetic ancestry and admixture within and between Colombian and other Latin American populations, and (2) exploring the relationship between ancestry and genetic determinants of health and disease in the region.…”

Socioeconomic deprivation and genetic ancestry interact to modify type 2 diabetes ethnic disparities in the United Kingdom

“…In the UK, SED has been associated with a greater T2D prevalence among minority Asian and Black populations than among those identifying as White [ 16 , 17 ]. Genetic differences between ethnic groups, owing to their different ancestral origins, have also been associated with T2D disparities [11] .In the US and Latin America, both African and Native American genetic ancestry (GA) have been associated with T2D disparities in Black and Hispanic populations [ [18] , [19] , [20] , [21] , [22] ]. However, the inclusion of SED has been shown to attenuate the effect of GA on T2D status in these populations [ 11 , 20 , 22 ].…”

Populations, Traits, and Their Spatial Structure in Humans

“…For two populations in Colombia, Antioquia (Mestizo) and Choco (Afro-Columbian), Chande et al (2020) found an overall concordance across several traits (WHI, height, BMI, hair color, eye color, inflammatory bowel disease, ischemic stroke, mortality in heart failure, immunity to malaria) between PGS predictions and observed anthropometric and epidemiological profiles. The authors used SNP trait associations from the NHGRI-EBI GWAS catalog which includes all GWAS associations across a large number of traits and study populations.…”