Genetic variation and health in rural Caribbean village

Abstract

Bwa Mawego is a small-scale horticultural community (~500 people) on the island of Dominica that has been the site of a longitudinal health research project for more than 30 years. Cardiovascular diseases and metabolic health are growing local concerns. Here we analyze longitudinal growth data, cardiometabolic metrics, and genome-wide single nucleotide polymorphism (SNP) data from this population to investigate sources of variation in anthropometric and cardiometabolic outcomes. Mixed effect heritability models indicate that (1) variation in body mass index (BMI) is significantly shaped by genetic variation, and (2) variation between longitudinal BMI curves has not been consistently impacted by secular environmental trends from 1997 2017. In order to assess genetic variation in more detail, we first characterize the population structure and admixture in this Caribbean community using high-density SNP data and global reference samples in the Human Genome Diversity Panel. We detect four distinct family clusters and admixture from African, European, and Amerindian ancestral populations that occurred 5-6 generations ago (~130-150 years). Amerindian haplotypes represented in Bwa Mawego associate with deeply diverged lineages in Karitiana and Surui peoples, highlighting the regionally variable nature of admixture throughout the Caribbean and unique historical outcomes in Dominica. Genome-wide association tests of cardiometabolic phenotypes identify a genomic region of interest downstream of the ANK3 gene that associates with BMI in Bwa Mawego, after controlling for confounding variation from ancestral population structure and relatedness. Any functional relationship between ANK3 and BMI is currently uncharacterized, and there is unique potential to further explore complex gene-environment-phenotype landscapes in Bwa Mawego.