Dataset Information

A latent genetic subtype of major depression identified by whole-exome genotyping data in a Mexican-American cohort.

ABSTRACT: Identifying data-driven subtypes of major depressive disorder (MDD) is an important topic of psychiatric research. Currently, MDD subtypes are based on clinically defined depression symptom patterns. Although a few data-driven attempts have been made to identify more homogenous subgroups within MDD, other studies have not focused on using human genetic data for MDD subtyping. Here we used a computational strategy to identify MDD subtypes based on single-nucleotide polymorphism genotyping data from MDD cases and controls using Hamming distance and cluster analysis. We examined a cohort of Mexican-American participants from Los Angeles, including MDD patients (n=203) and healthy controls (n=196). The results in cluster trees indicate that a significant latent subtype exists in the Mexican-American MDD group. The individuals in this hidden subtype have increased common genetic substrates related to major depression and they also have more anxiety and less middle insomnia, depersonalization and derealisation, and paranoid symptoms. Advances in this line of research to validate this strategy in other patient groups of different ethnicities will have the potential to eventually be translated to clinical practice, with the tantalising possibility that in the future it may be possible to refine MDD diagnosis based on genetic data.

SUBMITTER: Yu C

PROVIDER: S-EPMC5534938 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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A latent genetic subtype of major depression identified by whole-exome genotyping data in a Mexican-American cohort.

Yu C C Arcos-Burgos M M Licinio J J Wong M-L ML

Translational psychiatry 20170516 5

Identifying data-driven subtypes of major depressive disorder (MDD) is an important topic of psychiatric research. Currently, MDD subtypes are based on clinically defined depression symptom patterns. Although a few data-driven attempts have been made to identify more homogenous subgroups within MDD, other studies have not focused on using human genetic data for MDD subtyping. Here we used a computational strategy to identify MDD subtypes based on single-nucleotide polymorphism genotyping data fr ...[more]

PMID: 28509902

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Project description:There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is 48% in MXL, 25% in CLM, and 13% in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern American ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas 16 thousand years ago (kya), supports that the MXL Ancestors split 12.2kya, with a subsequent split of the ancestors to CLM and PUR 11.7kya. The model also features effective populations of 62,000 in Mexico, 8,700 in Colombia, and 1,900 in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations.

Dataset Information

A latent genetic subtype of major depression identified by whole-exome genotyping data in a Mexican-American cohort.

Publications

A latent genetic subtype of major depression identified by whole-exome genotyping data in a Mexican-American cohort.

Similar Datasets

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