title: Large-scale genomics unveil polygenic architecture of human cortical surface area.
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.
authors.affiliation: Multimodal Imaging Laboratory, Department of Radiology, University of California San Diego, La Jolla, California 92037, USA.
authors.forename: Chi-Hua
authors.initials: CH
authors.lastname: Chen
authors.affiliation: 1] Department of Human Biology, J. Craig Venter Institute, San Diego, California 92037, USA. [2] Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Peng
authors.affiliation: 1] Multimodal Imaging Laboratory, Department of Radiology, University of California San Diego, La Jolla, California 92037, USA. [2] Department of Cognitive Science, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Schork
authors.affiliation: Multimodal Imaging Laboratory, Department of Radiology, University of California San Diego, La Jolla, California 92037, USA.
authors.forename: Min-Tzu
authors.initials: MT
authors.lastname: Lo
authors.affiliation: 1] Multimodal Imaging Laboratory, Department of Radiology, University of California San Diego, La Jolla, California 92037, USA. [2] Department of Cognitive Science, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Fan
authors.affiliation: 1] Multimodal Imaging Laboratory, Department of Radiology, University of California San Diego, La Jolla, California 92037, USA. [2] Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA. [3] Norwegian Center for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Multimodal Imaging Laboratory, Department of Radiology, University of California San Diego, La Jolla, California 92037, USA.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Desikan
authors.affiliation: Norwegian Center for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bettella
authors.affiliation: Multimodal Imaging Laboratory, Department of Radiology, University of California San Diego, La Jolla, California 92037, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Hagler
authors.affiliation: 1] NORMENT, KG Jebsen Centre for Psychosis Research, Department of Psychology, University of Oslo, 0424 Oslo, Norway. [2] NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, 0317 Oslo, Norway.
authors.forename: Lars T
authors.initials: LT
authors.lastname: Westlye
authors.affiliation: 1] Department of Psychiatry, University of California, San Diego, La Jolla, California 92093, USA. [2] VA San Diego Center of Excellence for Stress and Mental Health, La Jolla, California 92037, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Kremen
authors.affiliation: 1] Department of Cognitive Science, University of California, San Diego, La Jolla, California 92093, USA. [2] Department of Psychiatry, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Terry L
authors.initials: TL
authors.lastname: Jernigan
authors.affiliation: 1] Dr E. Martens Research Group of Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, 5021 Bergen, Norway. [2] NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Norway.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Le Hellard
authors.affiliation: 1] Dr E. Martens Research Group of Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, 5021 Bergen, Norway. [2] NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Norway.
authors.forename: Vidar M
authors.initials: VM
authors.lastname: Steen
authors.affiliation: 1] NORMENT, KG Jebsen Centre for Psychosis Research, Department of Psychology, University of Oslo, 0424 Oslo, Norway. [2] NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, 0317 Oslo, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Espeseth
authors.affiliation: Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Huentelman
authors.affiliation: 1] Department of Neuroscience, Norwegian University of Science and Technology (NTNU), 7489 Trondheim, Norway. [2] Department of Medical Imaging, St. Olav's University Hospital, 7006 Trondheim, Norway.
authors.forename: Asta K
authors.initials: AK
authors.lastname: Håberg
authors.affiliation: 1] Norwegian Center for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway. [2] Department of Psychiatric Research, Diakonhjemmet Hospital, 0319 Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
authors.affiliation: 1] NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Norway. [2] Department of Medical Genetics, Oslo University Hospital, 0424 Oslo, Norway.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: Norwegian Center for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: Department of Human Biology, J. Craig Venter Institute, San Diego, California 92037, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Schork
authors.affiliation: 1] Multimodal Imaging Laboratory, Department of Radiology, University of California San Diego, La Jolla, California 92037, USA. [2] Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA. [3] Department of Psychiatry, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002540:Cerebral Cortex / Q000033:anatomy & histology*; D002648:Child; D002675:Child, Preschool; D017124:Conserved Sequence; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014427:Twins / Q000235:genetics*; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics; D055815:Young Adult