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

نویسندگان

  • Chi-Hua Chen
  • Qian Peng
  • Andrew J. Schork
  • Min-Tzu Lo
  • Chun-Chieh Fan
  • Yunpeng Wang
  • Rahul S. Desikan
  • Francesco Bettella
  • Donald J. Hagler
  • Connor McCabe
  • Linda Chang
  • Natacha Akshoomoff
  • Erik Newman
  • Thomas Ernst
  • Peter Van Zijl
  • Joshua Kuperman
  • Sarah Murray
  • Cinnamon Bloss
  • Mark Appelbaum
  • Anthony Gamst
  • Wesley Thompson
  • Hauke Bartsch
  • Michael Weiner
  • Paul Aisen
  • Ronald Petersen
  • Clifford R. Jack Jr
  • William Jagust
  • John Q. Trojanowki
  • Arthur W. Toga
  • Laurel Beckett
  • Robert C. Green
  • Andrew J. Saykin
  • John Morris
  • Leslie M. Shaw
  • Zaven Khachaturian
  • Greg Sorensen
  • Maria Carrillo
  • Lew Kuller
  • Marc Raichle
  • Steven Paul
  • Peter Davies
  • Howard Fillit
  • Franz Hefti
  • Davie Holtzman
  • M. Marcel Mesulman
  • William Potter
  • Peter J. Snyder
  • Adam Schwartz
  • Tom Montine
  • Ronald G. Thomas
  • Michael Donohue
  • Sarah Walter
  • Devon Gessert
  • Tamie Sather
  • Gus Jiminez
  • Danielle Harvey
  • Matthew Bernstein
  • Nick Fox
  • Paul Thompson
  • Norbert Schuff
  • Charles DeCarli
  • Bret Borowski
  • Jeff Gunter
  • Matt Senjem
  • Prashanthi Vemuri
  • David Jones
  • Kejal Kantarci
  • Chad Ward
  • Robert A. Koeppe
  • Norm Foster
  • Eric M. Reiman
  • Kewei Chen
  • Chet Mathis
  • Susan Landau
  • Nigel J. Cairns
  • Erin Householder
  • Lisa Taylor-Reinwald
  • Virginia M.Y. Lee
  • Magdalena Korecka
  • Michal Figurski
  • Karen Crawford
  • Scott Neu
  • Tatiana M. Foroud
  • Steven Potkin
  • Li Shen
  • Kelley Faber
  • Sungeun Kim
  • Kwangsik Nho
  • Leon Thal
  • Richard Frank
  • Neil Buckholtz
  • Marilyn Albert
  • John Hsiao
  • Lars T. Westlye
  • William S. Kremen
  • Terry L. Jernigan
  • Stephanie Le Hellard
  • Vidar M. Steen
  • Thomas Espeseth
  • Matt Huentelman
  • Asta K. Håberg
  • Ingrid Agartz
  • Srdjan Djurovic
  • Ole A. Andreassen
  • Nicholas Schork
  • Anders M. Dale
چکیده

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.

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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015