Detecting the structure of haplotypes, local ancestry and excessive local European ancestry in Mexicans

TL;DR

This paper introduces a two-layer hidden Markov model for detecting haplotype structure and local ancestry in admixed individuals, outperforming existing methods especially for short ancestral segments, and reveals regions of excessive European ancestry in Mexicans linked to neurodevelopmental genes.

Contribution

The paper presents a novel two-layer hidden Markov model that improves local ancestry inference by modeling two scales of linkage disequilibrium, specifically tailored for admixed populations.

Findings

Identified five regions with excessive European ancestry in Mexicans.

Discovered a 1.1Mb region on Chromosome 2p23 linked to autism and schizophrenia.

Validated findings using independent Mexican samples from the 1000 Genomes Project.

Abstract

We present a two-layer hidden Markov model to detect structure of haplotypes for unrelated individuals. This allows modeling two scales of linkage disequilibrium (one within a group of haplotypes and one between groups), thereby taking advantage of rich haplotype information to infer local ancestry for admixed individuals. Our method outperforms competing state-of-art methods, particularly for regions of small ancestral track lengths. Applying our method to Mexican samples in HapMap3, we found five coding regions, ranging from $0.3 -1.3$ megabase (Mb) in lengths, that exhibit excessive European ancestry (average dosage > 1.6). A particular interesting region of 1.1Mb (with average dosage 1.95) locates on Chromosome 2p23 that harbors two genes, PXDN and MYT1L, both of which are associated with autism and schizophrenia. In light of the low prevalence of autism in Hispanics, this region warrants special attention. We confirmed our findings using Mexican samples from the 1000 genomes project. A software package implementing methods described in the paper is freely available at \url{http://bcm.edu/cnrc/mcmcmc}