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

Marian L. Hamshere, Stanley Zammit, Cross-Disorder Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticle (Academic Journal)

1251 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)984-994
Number of pages11
JournalNature Genetics
Volume45
Issue number9
Early online date11 Aug 2013
DOIs
Publication statusPublished - Sep 2013

Keywords

  • Genetic association study
  • Medical genetics
  • Schizophrenia

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    Hamshere, M. L., Zammit, 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