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

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Listed:
  • Chi-Hua Chen

    (Multimodal Imaging Laboratory, University of California San Diego)

  • Qian Peng

    (J. Craig Venter Institute
    The Scripps Research Institute)

  • Andrew J. Schork

    (Multimodal Imaging Laboratory, University of California San Diego
    University of California, San Diego)

  • Min-Tzu Lo

    (Multimodal Imaging Laboratory, University of California San Diego)

  • Chun-Chieh Fan

    (Multimodal Imaging Laboratory, University of California San Diego
    University of California, San Diego)

  • Yunpeng Wang

    (Multimodal Imaging Laboratory, University of California San Diego
    University of California, San Diego
    Norwegian Center for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo)

  • Rahul S. Desikan

    (Multimodal Imaging Laboratory, University of California San Diego)

  • Francesco Bettella

    (Norwegian Center for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo)

  • Donald J. Hagler

    (Multimodal Imaging Laboratory, University of California San Diego)

  • Lars T. Westlye

    (NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo
    NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital)

  • William S. Kremen

    (University of California, San Diego
    VA San Diego Center of Excellence for Stress and Mental Health)

  • Terry L. Jernigan

    (University of California, San Diego
    University of California, San Diego)

  • Stephanie Le Hellard

    (Dr E. Martens Research Group of Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital
    NORMENT, KG Jebsen Centre for Psychosis Research, University of Bergen)

  • Vidar M. Steen

    (Dr E. Martens Research Group of Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital
    NORMENT, KG Jebsen Centre for Psychosis Research, University of Bergen)

  • Thomas Espeseth

    (NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo
    NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital)

  • Matt Huentelman

    (Translational Genomics Research Institute)

  • Asta K. Håberg

    (Norwegian University of Science and Technology (NTNU)
    St. Olav’s University Hospital)

  • Ingrid Agartz

    (Norwegian Center for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo
    Diakonhjemmet Hospital)

  • Srdjan Djurovic

    (NORMENT, KG Jebsen Centre for Psychosis Research, University of Bergen
    Oslo University Hospital)

  • Ole A. Andreassen

    (Norwegian Center for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo)

  • Nicholas Schork

    (J. Craig Venter Institute)

  • Anders M. Dale

    (Multimodal Imaging Laboratory, University of California San Diego
    University of California, San Diego
    University of California, San Diego)

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 (h2∼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.

Suggested Citation

  • Chi-Hua Chen & Qian Peng & Andrew J. Schork & Min-Tzu Lo & Chun-Chieh Fan & Yunpeng Wang & Rahul S. Desikan & Francesco Bettella & Donald J. Hagler & Lars T. Westlye & William S. Kremen & Terry L. Jer, 2015. "Large-scale genomics unveil polygenic architecture of human cortical surface area," Nature Communications, Nature, vol. 6(1), pages 1-7, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8549
    DOI: 10.1038/ncomms8549
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