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Large-scale genomics unveil polygenic architecture of human cortical surface area

Academic Article
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Overview

authors

  • Chen, C. H.
  • Peng, Qian
  • Schork, A. J.
  • Lo, M. T.
  • Fan, C. C.
  • Wang, Y.
  • Desikan, R. S.
  • Bettella, F.
  • Hagler, D. J.
  • Pediatric Imaging Neurocognition and Genetics Study
  • Alzheimer's Disease Neuroimaging Initiative
  • Westlye, L. T.
  • Kremen, W. S.
  • Jernigan, T. L.
  • Le Hellard, S.
  • Steen, V. M.
  • Espeseth, T.
  • Huentelman, M.
  • Haberg, A. K.
  • Agartz, I.
  • Djurovic, S.
  • Andreassen, O. A.
  • Schork, Nicholas
  • Dale, A. M.

publication date

  • July 2015

journal

  • Nature Communications  Journal

abstract

  • Little is known about how genetic variation contributes to neuroanatomical variability, and whether particular genomic regions comprising genes or evolutionarily conserved elements are enriched for effects that influence brain morphology. Here, we examine brain imaging and single-nucleotide polymorphisms (SNPs) data from ∼2,700 individuals. We show that a substantial proportion of variation in cortical surface area is explained by additive effects of SNPs dispersed throughout the genome, with a larger heritable effect for visual and auditory sensory and insular cortices (h(2)∼0.45). Genome-wide SNPs collectively account for, on average, about half of twin heritability across cortical regions (N=466 twins). We find enriched genetic effects in or near genes. We also observe that SNPs in evolutionarily more conserved regions contributed significantly to the heritability of cortical surface area, particularly, for medial and temporal cortical regions. SNPs in less conserved regions contributed more to occipital and dorsolateral prefrontal cortices.

subject areas

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Cerebral Cortex
  • Child
  • Child, Preschool
  • Conserved Sequence
  • Female
  • Genome, Human
  • Genomics
  • Genotype
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuroimaging
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Twins
  • Twins, Dizygotic
  • Twins, Monozygotic
  • Young Adult
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Identity

PubMed Central ID

  • PMC4518289

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms8549

PubMed ID

  • 26189703
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Additional Document Info

start page

  • 7549

volume

  • 6

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