John Capra
Last active: 3/3/2020

Local ancestry transitions modify snp-trait associations.

Fish AE, Crawford DC, Capra JA, Bush WS
Pac Symp Biocomput. 2018 23: 424-435

PMID: 29218902 · PMCID: PMC5728664

Genomic maps of local ancestry identify ancestry transitions - points on a chromosome where recent recombination events in admixed individuals have joined two different ancestral haplotypes. These events bring together alleles that evolved within separate continential populations, providing a unique opportunity to evaluate the joint effect of these alleles on health outcomes. In this work, we evaluate the impact of genetic variants in the context of nearby local ancestry transitions within a sample of nearly 10,000 adults of African ancestry with traits derived from electronic health records. Genetic data was located using the Metabochip, and used to derive local ancestry. We develop a model that captures the effect of both single variants and local ancestry, and use it to identify examples where local ancestry transitions significantly interact with nearby variants to influence metabolic traits. In our most compelling example, we find that the minor allele of rs16890640 occuring on a European background with a downstream local ancestry transition to African ancestry results in significantly lower mean corpuscular hemoglobin and volume. This finding represents a new way of discovering genetic interactions, and is supported by molecular data that suggest changes to local ancestry may impact local chromatin looping.

MeSH Terms (16)

Adult African Continental Ancestry Group Chromosomes, Human Computational Biology Epistasis, Genetic European Continental Ancestry Group Evolution, Molecular Gene Frequency Genetics, Population Genome-Wide Association Study Haplotypes Humans Linear Models Models, Genetic Polymorphism, Single Nucleotide Recombination, Genetic

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