Five major mental illnesses — depression, bipolar disorder, ADHD, schizophrenia and autism — are traceable to the same inherited genetic variations, according to the largest genome-wide study of its kind. These variations account for 17-28 percent of mental illness risk.
The study revealed that the overlap is highest between schizophrenia and bipolar disorder; moderate for bipolar and depression, and for ADHD and depression; and low between schizophrenia and depression.
“Since our study only looked at common gene variants, the total genetic overlap between the disorders is likely higher,” said Naomi Wray, Ph.D., University of Queensland, Brisbane, Australia.
“Shared variants with smaller effects, rare variants, mutations, duplications, deletions, and gene-environment interactions also contribute to these illnesses.”
The overlap in heritability that could be attributed to common genetic variation was about 15 percent between schizophrenia and bipolar disorder, about 10 percent between bipolar disorder and depression, about 9 percent between schizophrenia and depression, and about 3 percent between schizophrenia and autism.
“Such evidence quantifying shared genetic risk factors among traditional psychiatric diagnoses will help us move toward classification that will be more faithful to nature,” said Bruce Cuthbert, Ph.D., director of the NIMH Division of Adult Translational Research and Treatment Development.
Earlier this year, researchers with the Psychiatric Genomics Consortium (PGC) — over 300 scientists at 80 research centers in 20 countries—reported the first evidence of overlap between all five disorders.
Individuals with these disorders were more likely to have suspect variation at the same four chromosomal sites. The extent of the overlap, however, remained unclear.
In the new study, researchers used the same genome-wide information and the largest amounts of data currently available to calculate the risk for these mental disorders. They evaluated whether they could be attributable to any of hundreds of thousands of sites of common variability in the genetic code across chromosomes.
The researchers looked for similarities in genetic variations among thousands of people with each illness and compared them to controls, figuring out how much each pair of disorders is linked to the same genetic variants.
The new evidence linking schizophrenia and depression, if replicated, could have important implications for diagnostics and research, say the researchers. They expected to see more overlap between ADHD and autism, but the modest schizophrenia-autism connection is consistent with other emerging evidence.
The findings still leave much of the likely inherited genetic contribution to the disorders unexplained – and especially the non-inherited genetic factors. For example, common genetic variation accounted for 23 percent of schizophrenia, but evidence from twin and family studies estimate its total heritability at 81 percent.
“It is encouraging that the estimates of genetic contributions to mental disorders trace those from more traditional family and twin studies. The study points to a future of active gene discovery for mental disorders,” said Thomas Lehner, Ph.D., chief of the NIMH Genomics Research Branch.
Source: Nature Genetics