Extensive genome analysis identifies differences by sex in major psychiatric disorders

In a multinational study, researchers scanned the genomes of nearly 200,000 people to find interactions with the genes and sex of schizophrenia, major depressive disorder and bipolar disorder.

Boston – An analysis of gender differences in the genetics of schizophrenia, bipolar disorder, and major depressive disorders indicates that while there is significant genetic overlap between males and females, there are marked gender-dependent differences in how genes relate to the central nervous system and immunity. Suffering from these disorders.

Findings by a multinational consortium of psychiatric researchers including investigators and a senior writer at Massachusetts General Hospital (MGH), could catalyze better treatments for major mental disorders. It was published in the journal Biological Psychiatry.

The results were only possible through the collaboration of more than 100 researchers and research groups, who combed the genomes of 33,403 people with schizophrenia, 19,924 with bipolar disorder, 32,408 with major depressive disorder, as well as 109,946 people with schizophrenia. From these diagnoses).

Their goal was to understand why these major mental disorders differ between the sexes. For example, women are more likely to have major depressive disorder, while the risk of developing schizophrenia is much higher among men. The risk of developing bipolar disorder is roughly the same for both women and men, but the onset of the disease, of course, and the prognosis differ markedly between the two.

“We are in the era of big data, and we are searching for disease-related genes to determine drug targets linked to the genotype, in order to develop more effective treatments for this disease that may differ by gender,” says Gil M.

Goldstein and colleagues searched for evidence in the form of single nucleotide polymorphisms, or SNPs (“snips”), where the “letter” of a single DNA (nucleotide) differs from person to person and between genders.

There are gender differences in the frequency of chronic diseases and cancers as well. “It’s pervasive,” says Goldstein, who is also professor of psychiatry and medicine at Harvard Medical School. But medicine is mainly built on models of male health and male animal models. We need to develop our precision medicine models that incorporate gender influence. “

By making use of large psychological databases, researchers were able to demonstrate that the risks of schizophrenia, bipolar disorder, and major depressive disorder are influenced by the interactions of certain genes with sex, regardless of the effects of sex hormones such as estradiol or testosterone.

For example, researchers have found interactions with schizophrenia, depression, and sexuality in genes that control production of endothelial growth factor, a protein that promotes the growth of new blood vessels.

“My lab studies the high frequency of depression and cardiovascular disease. It turns out that both depression and schizophrenia have a very high relationship with cardiovascular disease. We think there are common causes between mental illness and cardiovascular disease that are not due to the effects of drugs.” The incidence of depression and cardiovascular disease is twice as high in women as in men, and this may be partly related to what we have found in depression of the sex differences in a gene that controls the growth factor of the endothelium of blood vessels. ”

The researchers emphasize that although the exact causes of the diseases they studied remain unknown, “our study underscores the importance of designing large-scale genetic studies with statistical power to test interactions with sex. Anatomy of the effect of gender, genetics, and pathophysiology will define potential targets for sex-dependent therapeutic interventions Or sex-specific, which creates more effective treatments for both men and women, “she says.


The analyzes were supported by private donor Joel York, the National Institute of Mental Health, and the National Institutes of Health Office of Women’s Health Research.

About Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the largest teaching hospital at Harvard Medical School. Mass General Research Institute conducts the nation’s largest hospital-based research program, with annual searches of more than $ 1 billion and involving more than 9,500 researchers working in more than 30 institutes, centers and departments. In August 2020, Mass General was ranked 6th in US News and World Report List of “America’s Best Hospitals”.

Media contact
Noah Brown
[email protected]http: // dx.Resonate.Deer /10.1016 /J.Biopsy.2021.02.972

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