shared genetics of five psychiatric disorders. Lancet. 2013 (ahead of print)

12.03.2013

The mechanisms that cause psychiatric disorders are largely unknown. We define various disorders based on consensus. The boundaries of disorders continue to change as  new evidence emerge. Debates continue on how best to classify mental disorders .

Genome wide association studies (GWAS) provide an opportunity to see how disorders are linked at a molecular level. Huge growth in genome wide data has increased the power for detection of trait-associated variants.  Psychiatric Genomics Consortium (PGC) was formed in 2007 and the Cross-Disorder Group of the PGC is now reporting on the  information that emerge when all five disorders (ADHD,Autism,bipolar disorder, Major depressive disorder and schizophrenia) are examined in one GWAS.  They also tested  the cross-disorder effects of variants already identified as being associated with a specific psychiatric disorder in previous PGC analyses. The group analysed  genome-wide single nucleotide polymorphism (SNP) data for 33332 cases and 27888 controls distributed among the above major psychiatric disorders using data from more than 19 countries ( European ancestry) .

Findings: SNPs at four loci—regions on chromosomes 3p21 and 10q24, and SNPs in two L-type voltage-gated calcium-channel subunits, CACNA1C and CACNB2—exceeded the cutoff for genome-wide signifi- cance in the primary analysis.  The strongest signal was within a region on chromosome 3p21.1.Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Results suggest that voltage-gated calcium signalling ( calcium-channel activity) could be an important biological process in all these five psychiatric disorders.Some SNPs showing diagnostic specificity and others pleiotropic effects on two or more of the five disorders.

Conclusions:

Specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. The findings support the common co-occurrence of clinical phenotypes in individual patients. Variation in Calcium-channel signalling genes could be  important in basic molecular mechanism of all these disorders.  This pathway has the potential to be a therapeutic target for psychiatric disease.

Summary of the article:

Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Cross-Disorder Group of the Psychiatric Genomics Consortium. Lancet. 2013 Feb 27. doi:pii: S0140-6736(12)62129-1. 10.1016/S0140-6736(12)62129-1. [Epub ahead of print]

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