Recent fluctuations in Mexican American genomes have altered the genetic architecture of biomedical traits

Hispanics/Latinos are a diverse group of admixed populations with African, European, and Native American ancestries. They remain understudied, and thus little is known about the genetic architecture of phenotypic variation in these populations. Using genome-wide genotype data from the Hispanic Community Health Study/Study of Latinos, we find that Native American ancestry has increased over time across Hispanic/Latino populations, particularly in Mexican Americans where Native American ancestry increased by an average of ∼20% over the 50-year period spanning 1940s-1990s. We find similar patterns across American cities, and replicate our observations in an independent sample of Mexican Americans. These dynamic ancestry patterns are a result of a complex interaction of several population and cultural factors, including strong ancestry-related assortative mating and subtle shifts in migration with differences in subcontinental Native American ancestry over time. These factors have shaped patterns of genetic variation, including an increase in runs of homozygosity in Native American ancestral tracts, and also influenced the genetic architecture of complex traits within the Mexican American population. We show for height, a trait correlated with ancestry, polygenic risk scores based on summary statistics from a European-based genome-wide association study perform poorly in Mexican Americans. Our findings reveal temporal changes in population structure within Hispanics/Latinos that may influence biomedical traits, demonstrating a crucial need to improve our understanding of the genetic diversity of admixed populations.