Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
Lancet. 2013 Apr 20;381(9875):1371-9.
Cross-Disorder Group of the Psychiatric Genomics Consortium.
Erratum in: Lancet. 2013 Apr 20;381(9875):1360.
Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories.
We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.
We analyzed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders
SNPs at four loci surpassed the cutoff for genome-wide significance (p<5×10(-8)) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2.
Model selection analysis supported effects of these loci for several disorders.
Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity.
Pathway analysis supported a role for calcium channel signalling genes for all five disorders.
Our findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology.
These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause.
Genes and the Human Condition (From Behavior to Biotechnology)