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Common genetic basis found for five major psychiatric illnesses

Robin Wulffson MD's picture
genetics, bipolar disorder, schizophrenia, autism, ADHD, depression

Psychiatric illnesses have long been believed to have a genetic component. A new study has not only reinforced that concept but also found that five major psychiatric illnesses share a common genetic basis. The findings may lead to new treatments for these disorders. The study was published by researchers affiliated with Massachusetts General Hospital (Boston, Massachusetts) online on February 28 in The Lancet.

The researchers attribute the outcome of their research to data obtained from the National Human Genome Research Institute database of published genome-wide association studies (GWAS); since 2005, the GWAS has accumulated more than 5,110 entries for over 500 traits. The study authors note that the rapid growth of data repositories has enabled researchers to undertake large studies and meta-analyses, and has increased the power for detection of trait-associated variants. The new study describes an analysis of genome-wide single nucleotide polymorphism (SNP) data for 33,332 cases and 27,888 controls distributed among five major psychiatric disorders: major depressive disorder, bipolar disorder, schizophrenia, autism spectrum disorders, and attention deficit hyperactivity disorder (ADHD). Thus, these five major psychiatric disorders actually share common genetic risk factors.

Currently, the standard practice for diagnosing a psychiatric disorder typically involves behavior rather than biology. A person exhibiting symptoms of hyperactivity and inattentiveness may be prescribed medication for attention deficit-hyperactivity disorder, while those alternating between periods of intense happiness and depression may be showing signs of bipolar disorder.
However, scientists have theorized for some time that genetic variations may play key roles in the development of these types of psychiatric disorders. The new study presents DNA evidence that this theory is not only to be true but also that many unrelated disorders are more connected than previously thought.

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Rather than sequencing each individual’s entire genome, the researchers used DNA chips, which covered any variations across the genome. With their analysis, the investigators ultimately identified four risk loci that appeared to have a significant link to the five psychiatric disorders: regions on chromosomes 3p21 and 10q24, along with the nucleotide polymorphisms (SNPs) in two genes involved in regulating the flow of calcium in the brain (CACNA1C, linked to bipolar disorder and schizophrenia in previous research and CACNB2).

When cross-examining the genomes, the researchers calculated each variants polygenic (multiple gene) risk scores. Among the adult-onset disorders (bipolar, schizophrenia and depressive disorder), the scores were the strongest. However, overall, some variants seem to play more of a key role than others. Lead author Dr. Jordan Smoller explained that each variant has a certain frequency and that the frequency of the variant that increases risk ranged from 10-35%. He explained that those percentages represent a fairly common genetic risk factor. However, while the study authors feel that these genetic variants do play key roles in the development of both child and adult-onset disorders, the overall causes for psychiatric illness are multi-factorial. By themselves, these DNA variants are not responsible for the onset of these disorders, and it is possible for an individual to possess all of these genetic variations and not have any of these conditions.

Dr. Smoller noted that the main take home message from their research was that scientists have yet to truly understand why a person develops a psychiatric disorder. This new research can hopefully provide healthcare professionals with a better understanding of what causes psychiatric illness and help researchers develop more targeted therapies in the future.

Reference: The Lancet