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Early developmental gene enhancers affect subcortical volumes in the adult human brain.

ABSTRACT: Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P?=?0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P?

SUBMITTER: Becker M

PROVIDER: S-EPMC4883000 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Early developmental gene enhancers affect subcortical volumes in the adult human brain.

Becker Martin M Guadalupe Tulio T Franke Barbara B Hibar Derrek P DP Renteria Miguel E ME Stein Jason L JL Thompson Paul M PM Francks Clyde C Vernes Sonja C SC Fisher Simon E SE

Human brain mapping 20160218 5

Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selectin ...[more]

PMID: 26890892

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Early developmental gene enhancers affect subcortical volumes in the adult human brain.

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Early developmental gene enhancers affect subcortical volumes in the adult human brain.

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