Five Major Psychiatric Disorders Share Common Genetics

Autism, attention deficit-hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder, and schizophrenia all share common genetic underpinnings, according to a new study.

Researchers at Massachusetts General Hospital (MGH; Boston, USA) analyzed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33,332 cases and 27,888 controls of European ancestry. The researchers characterized the cross-disorder effects of significant loci—previously identified for bipolar disorder and schizophrenia—and used polygenic risk-score analysis to examine the effects from a broader set of common variants. Pathway analyses were then used to establish the biological associations underlying the genetic overlap for the five disorders.

The results showed that SNPs on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits (CACNA1C and CACNB2), surpassed the cutoff for genome-wide significance in the primary analysis. Model selection supported the effects of these loci for several disorders, and polygenic risk scores showed cross-disorder associations, notably among adult-onset disorders. Pathway analysis supported a role for calcium channel signaling genes for all five disorders, and SNPs with evidence of cross-disorder association were enriched for expression quantitative trait loci (eQTL) markers in the brain. The study was published early online on February 28, 2013, in the Lancet.

“Our results suggest that voltage-gated calcium signaling, and, more broadly, calcium-channel activity, could be an important biological process in psychiatric disorders,” concluded lead author Jordan Smoller, MD, ScD, and colleagues. “The calcium-channel gene CACNA1C has been previously linked to bipolar disorder, schizophrenia, and major depressive disorder, as well as to Timothy syndrome, a developmental disorder that can include autism. The other calcium-channel gene has been linked to bipolar disorder in people of Han Chinese ethnicity.”

A SNP is a DNA sequence variation occurring when a single nucleotide in the genome differs between paired chromosomes, such as two sequenced DNA fragments from different individuals. SNPs occur in noncoding regions more frequently than in coding regions, or where natural selection is acting and fixating the allele of the SNP that constitutes the most favorable genetic adaptation; for example, affecting how humans develop diseases and how they respond to pathogens, chemicals, drugs, vaccines, and other agents.

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