Ripke, Stephan4; Neale, Benjamin M.4; Corvin, Aiden12; Walters, James T. R.13; Farh, Kai-How4; Holmans, Peter A.13; Lee, Phil4; Bulik-Sullivan, Brendan4; Collier, David A.7; Huang, Hailiang4; Pers, Tune Hannes1; Agerbo, Esben8; Demontis, Ditte9; Hansen, Thomas10; Hollegaard, Mads Vilhelm14; Hougaard, David M.14; Mors, Ole8; Werge, Thomas10
1 Department of Systems Biology, Technical University of Denmark2 Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark3 Behavioral Phenomics, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark4 Massachusetts General Hospital5 Trinity College Dublin6 Cardiff University7 King’s College London8 Aarhus University9 The Lundbeck Foundation Initiative for Integrative Psychiatric Research10 Copenhagen University Hospital11 Statens Serum Institut12 Trinity College Dublin13 Cardiff University14 Statens Serum Institut
Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, andare consistent with leadingpathophysiologicalhypotheses. Independentof genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
Nature, 2014, Vol 511, Issue 7510, p. 421-427
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't