Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Lee, S Hong and Ripke, Stephan and Neale, Benjamin M and Faraone, Stephen V and Purcell, Shaun M and Perlis, Roy H and Mowry, Bryan J and Thapar, Anita and Goddard, Michael E and Witte, John S and Absher, Devin and Agartz, Ingrid and Akil, Huda and Amin, Farooq and Andreassen, Ole A and Anjorin, Adebayo and Anney, Richard and Anttila, Verneri and Arking, Dan E and Asherson, Philip and Azevedo, Maria H and Backlund, Lena and Badner, Judith A and Bailey, Anthony J and Banaschewski, Tobias and Barchas, Jack D and Barnes, Michael R and Barrett, Thomas B and Bass, Nicholas and Battaglia, Agatino and Bauer, Michael and Bayés, Mònica and Bellivier, Frank and Bergen, Sarah E and Berrettini, Wade and Betancur, Catalina and Bettecken, Thomas and Biederman, Joseph and Binder, Elisabeth B and Black, Donald W and Blackwood, Douglas H R and Bloss, Cinnamon S and Boehnke, Michael and Boomsma, Dorret I and Breen, Gerome and Breuer, René and Bruggeman, Richard and Cormican, Paul and Buccola, Nancy G and Pickard, Benjamin S, Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, 45 (9). 984–994. (https://doi.org/10.1038/ng.2711)

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Abstract

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

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