Large-scale genomics unveil polygenic architecture of human cortical surface area
Chen, Chi-Hua; Peng, Qian; Schork, Andrew J.; Lo, Min-Tzu; Fan, Chun-Chieh; Wang, Yunpeng; Desikan, Rahul S.; Bettella, Franscesco; Hagler, Donald J.; Westlye, Lars Tjelta; Kremen, William S.; Jernigan, Terry L.; Le Hellard, Stephanie; Steen, Vidar Martin; Espeseth, Thomas; Huentelman, Matt; Håberg, Asta; Agartz, Ingrid; Djurovic, Srdjan; Andreassen, Ole Andreas; Schork, Nicholas; Dale, Anders
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 B2,700 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 (h2B0.45). Genome-wide SNPs collectively account for, on
average, about half of twin heritability across cortical regions (N¼466 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.