Recent shifts in the genomic ancestry of Mexican Americans may alter the genetic architecture of biomedical traits

Abstract

People in the Americas represent a diverse continuum of populations with varying degrees of admixture among African, European, and Amerindigenous ancestries. In the United States, populations with non-European ancestry remain understudied, and thus little is known about the genetic architecture of phenotypic variation in these populations. Using genotype data from the Hispanic Community Health Study/Study of Latinos, we find that Amerindigenous ancestry increased by an average of ~20% spanning 1940s-1990s in Mexican Americans. These patterns result from complex interactions between several population and cultural factors which shaped patterns of genetic variation and influenced the genetic architecture of complex traits in Mexican Americans. We show for height how 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 need to improve our understanding of admixed populations.

Human genetic admixture through the lens of population genomics

“…Similarly, sociocultural practices that govern mate choice or sex-specific contributions from the source populations will leave signatures in patterns of genetic ancestry. Individual behaviours such as mating preferences or long-range migration can exhibit ancestry biases in which the ancestry patterns in the subset of the population that migrates are not representative of the whole admixed population, potentially driven by correlations between ancestry and visible traits like skin pigmentation or socioeconomic differences [64][65][66][67][68][69]. Simple models of admixture often assume that individuals mate randomly; however, admixed human populations show evidence of positive assortative mating, with mating pairs often correlated in global ancestry proportion [67,[70][71][72].…”

“…Similarly, temporal changes in ancestry proportion within a population may be caused by time-varying social dynamics. Spear et al [69] found a significant increase in Amerindigenous ancestry in Mexican American populations over time, potentially owing to differences in ancestry in the migrating population over time and fecundity correlated with ancestry.…”

Disparities in acute lymphoblastic leukemia risk and survival across the lifespan in the United States of America

“…PhenoGram plots [140] were constructed for genetic variants associated with (A) ALL susceptibility, and/or (B) ALL patient outcomes (i.e., relapse and response to therapy). Genetic variants included in the PhenoGrams were identified in the NHGRI-EBI catalog of human genome-wide association studies (GWAS Catalog) [141] and included in published GWAS for acute lymphoblastic leukemia (ALL) [15,16,[18][19][20][24][25][26][27]32,135,136] or for outcomes of ALL [142][143][144][145][146][147][148][149][150] . We also included some variants described in additional papers included in this review for ALL susceptibility [17,[21][22][23][28][29][30][31] and ALL patient outcomes [21,139] .…”

Fanconi Anemia Patients from an Indigenous Community in Mexico Carry a New Founder Pathogenic Variant in FANCG

“…Finally, to ascertain that our patients share the Mexican population (MXL) genetic background, as reported in the 1KGP, a global ancestry analysis was performed. In this context and considering that Mexicans present a remarkable genetic diversity due to population admixture, we decided to contrast all SNVs data of these 3 Mixe patients against other populations beside the MXL, including Native-Americans (NAT), Utah residents with Northern and Western European ancestry (CEU), and Yoruba in Ibadan, Nigeria (YRI); similar to how the Mexican population structure has been analyzed in previous studies [25,26]. Using this appoach, it was observed that the MXL population presents an ancestry pattern with native and european components predominance (NAT:46.59% and CEU:48.44%, respectively).…”