Large-scale genetic analysis across disorders

An international study has identified extensive genetic overlap across 14 psychiatric disorders, helping explain why multiple diagnoses are common over a person’s lifetime. The research, published on December 10 in Nature, analyzed genetic data from more than 6 million individuals, including over 1 million people with a childhood or adult psychiatric disorder and about 5 million individuals without a diagnosis. The study is the latest effort from the Psychiatric Genomics Consortium Cross-Disorder Working Group, co-chaired by Kenneth Kendler, a professor in the Department of Psychiatry at Virginia Commonwealth University School of Medicine, and Jordan Smoller, a professor in the Department of Psychiatry at Harvard Medical School.

Five genetically related disorder groups

Using multiple analytical approaches, the researchers identified 428 genetic variants linked to more than one disorder and 101 chromosomal regions where shared variants were concentrated. Statistical modeling showed that the 14 conditions clustered into five genetically related groups covering compulsive disorders, internalizing disorders, neurodevelopmental disorders, schizophrenia and bipolar disorder, and substance use disorders. Major depression, anxiety disorders, and post-traumatic stress disorder showed especially strong overlap, with about 90% of genetic risk shared across these conditions. Schizophrenia and bipolar disorder shared roughly two thirds of their genetic markers.

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Implications for psychiatric research and care

According to the researchers, disorders with greater genetic overlap also showed similarities in when shared genes were active during human development and which brain cell types were involved. Internalizing disorders were more closely linked to genes expressed in oligodendrocytes, while schizophrenia and bipolar disorder were more associated with genes expressed in excitatory neurons. The findings provide a genetic framework for understanding comorbidity in psychiatry and may inform future research into treatments for conditions that frequently occur together.

Source: VCU

The Psychiatric Genomics Consortium study, a large and diverse genetics study based in the UK, has identified large numbers of specific genes that influence schizophrenia. This comes from DNA analysis of over 320,000 people, which showed that genetic risk for schizophrenia is seen in genes concentrated in neurons in the brain, but not in any other tissue or brain cells.

Neuroscientists from Cardiff University, who led the study, said the newfound genetic associations would help in understanding the causes of this psychiatric disorder and developing new treatments.

Schizophrenia is a debilitating disorder characterised by hallucinations, delusions, and problems with thinking clearly. It starts in late adolescence or early adulthood and at any one time affects around one in 300 people worldwide, according to the World Health Organization (WHO).

Of the myriad of genomic regions associated with schizophrenia, the neuroscientists identified 120 genes expressed in neurons likely to contribute to schizophrenia – abnormal neuron function is what causes symptoms.

A companion study involving many of the same neuroscientists and other researchers including those from Harvard and MIT, additionally found mutations in genes that, while very rare, have large effects on the small proportion of people that carry them. They also found overlapping genes and aspects of biology.

“Whilst people with schizophrenia can recover, many do not respond well to treatments, experience long-term problems with their mental and physical health, as well as impacts on relationships, education and work,” said Professor James Walters, Director of the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University.

“We hope the findings in this, and the companion studies, can be used to advance our understanding of the disorder and facilitate the development of radically new treatments. However, those processes are often not straightforward, and a lot of work by other neuroscientists is needed to translate the genetic findings into a detailed understanding of disease mechanisms.”

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