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Chen, C.H.; Peng, Q.; Schork, A.J.; Lo, M.T.; Fan, C.C.; Wang, Y.; Desikan, R.S.; Bettella, F.; Hagler, D.J.; Westlye, L.T.; Kremen, W.S.; Jernigan, T.L.; Hellard, S.L.; Steen, V.M.; Espeseth, T.; Huentelman, M.; Haberg, A.K.; Agartz, I.; Djurovic, S.; Andreassen, O.A.; Schork, N.; Dale, A.M. |
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Large-scale genomics unveil polygenic architecture of human cortical surface area |
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Journal Article |
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2015 |
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Nat Commun |
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Nature communications |
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6 |
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7549 |
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HUNT3; Adolescent; Adult; Aged; Aged, 80 and over; Base Sequence; Cerebral Cortex/*anatomy & histology; Child; Child, Preschool; Conserved Sequence; Female; Genome, Human/*genetics; *Genomics; Genotype; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Phenotype; Polymorphism, Single Nucleotide; Twins/*genetics; Twins, Dizygotic/genetics; Twins, Monozygotic/genetics; Young Adult |
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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 approximately 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) approximately 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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Multimodal Imaging Laboratory, Department of Radiology, University of California San Diego, La Jolla |
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Notes |
Chen, Chi-HuaPeng, QianSchork, Andrew JLo, Min-TzuFan, Chun-ChiehWang, YunpengDesikan, Rahul SBettella, FrancescoHagler, Donald JPediatric Imaging, Neurocognition and Genetics StudyAlzheimer's Disease Neuroimaging InitiativeWestlye, Lars TKremen, William SJernigan, Terry LHellard, Stephanie LeSteen, Vidar MEspeseth, ThomasHuentelman, MattHaberg, Asta KAgartz, IngridDjurovic, SrdjanAndreassen, Ole ASchork, NicholasDale, Anders MPediatric Imaging Neurocognition and Genetics StudyEnglandNat Commun. 2015 Jul 20;6:7549. doi: 10.1038/ncomms8549. |
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HUNT @ maria.stuifbergen @ Chen2015 |
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1799 |
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