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Large-scale genome analysis identifies differences by sex in major psychiatric disorders

Date:
March 23, 2021
Source:
Massachusetts General Hospital
Summary:
Psychiatric researchers have identified interactions between genes and sex that might partly explain how major psychiatric disorders affect males and females differently.
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性别差异的遗传学的分析schizophrenia, bipolar disorder and major depressive disorders indicates that while there is substantial genetic overlap between males and females, there are noticeable sex-dependent differences in how genes related to the central nervous system, immune system, and blood vessels affect people with these disorders.

The findings, from a multinational consortium of psychiatric researchers including investigators and a senior author at Massachusetts General Hospital (MGH), could spur better treatments for major psychiatric disorders. They are published in the journalBiological Psychiatry.

The findings were made possible only through the cooperation of more than 100 investigators and research groups, who combed through the genomes of 33,403 people with schizophrenia, 19,924 with bipolar disorder, and 32,408 with major depressive disorder, as well as 109,946 controls (people without any of these diagnoses).

Their goal was to understand why these major psychiatric disorders differed between the sexes. For example, women have a significantly higher risk for major depressive disorder, whereas the risk for schizophrenia is significantly higher among men. The risk of bipolar disorder is about the same for both women and men, but disease onset, course, and prognosis differ markedly between the two.

"We're in the era of Big Data, and we're looking for genes that are associated with illnesses to identify druggable targets associated with the genotype, in order to develop more effective treatments for that illness that may differ by sex," says senior author Jill M. Goldstein, PhD, founder and executive director of the Innovation Center on Sex Differences in Medicine (ICON) at MGH.

Goldstein and colleagues searched for clues in the form of single nucleotide polymorphisms, or SNPs ("snips"), in which a single DNA "letter" (nucleotide) differs from one person to the next and between sexes.

"There are sex differences in the frequency of chronic diseases and cancers as well. It's pervasive," says Goldstein, who is also a professor of Psychiatry and Medicine at Harvard Medical School. "But medicine, essentially, has been built on models of men's health and male animals. We need to develop our precision medicine models incorporating the effect of sex."

By taking advantage of large psychiatric databases, the investigators were able to demonstrate that the risks for schizophrenia, bipolar disorder and major depressive disorder are affected by interactions of specific genes with sex, apart from the effects of sex hormones such as estradiol or testosterone.

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For example, the investigators found interactions with schizophrenia and depression and sex in genes controlling for the production of vascular endothelial growth factor, a protein that promotes the growth of new blood vessels.

"My lab is studying the substantial co-occurrence of depression and cardiovascular disease. It turns out that both depression and schizophrenia have a very high co-occurrence with cardiovascular disease. We believe there are shared causes between psychiatric and cardiovascular diseases that are not due to the effects of medication," she says. "In addition, the co-occurrence of depression and cardiovascular disease is twice as high in women as in men, and this may, in part, be associated with our finding in depression of sex differences in a gene controlling vascular endothelial growth factor."

The investigators emphasize that although the specific causes of the diseases they studied are still unknown, "our study underscores the importance of designing large-scale genetic studies that have the statistical power to test for interactions with sex. Dissecting the impact of sex, genes, and pathophysiology will identify potential targets for sex-dependent or sex-specific therapeutic interventions creating more effective therapies for both men and women," she says.

The analyses were supported by private donor Gwill York, the National Institute of Mental Health and the NIH Office for Research on Women's Health.

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Materialsprovided byMassachusetts General Hospital.注意:内容可能被编辑风格d length.


Journal Reference:

  1. Gabriëlla A.M. Blokland, Jakob Grove, Chia-Yen Chen, Chris Cotsapas, Stuart Tobet, Robert Handa, David St Clair, Todd Lencz, Bryan J. Mowry, Sathish Periyasamy, Murray J. Cairns, Paul A. Tooney, Jing Qin Wu, Brian Kelly, George Kirov, Patrick F. Sullivan, Aiden Corvin, Brien P. Riley, Tõnu Esko, Lili Milani, Erik G. Jönsson, Aarno Palotie, Hannelore Ehrenreich, Martin Begemann, Agnes Steixner-Kumar, Pak C. Sham, Nakao Iwata, Daniel R. Weinberger, Pablo V. Gejman, Alan R. Sanders, Joseph D. Buxbaum, Dan Rujescu, Ina Giegling, Bettina Konte, Annette M. Hartmann, Elvira Bramon, Robin M. Murray, Michele T. Pato, Jimmy Lee, Ingrid Melle, Espen Molden, Roel A. Ophoff, Andrew McQuillin, Nicholas J. Bass, Rolf Adolfsson, Anil K. Malhotra, Nicholas G. Martin, Janice M. Fullerton, Philip B. Mitchell, Peter R. Schofield, Andreas J. Forstner, Franziska Degenhardt, Sabrina Schaupp, Ashley L. Comes, Manolis Kogevinas, José Guzman-Parra, Andreas Reif, Fabian Streit, Lea Sirignano, Sven Cichon, Maria Grigoroiu-Serbanescu, Joanna Hauser, Jolanta Lissowska, Fermin Mayoral, Bertram Müller-Myhsok, Beata Świątkowska, Thomas G. Schulze, Markus M. Nöthen, Marcella Rietschel, John Kelsoe, Marion Leboyer, Stéphane Jamain, Bruno Etain, Frank Bellivier, John B. Vincent, Martin Alda, Claire O’Donovan, Pablo Cervantes, Joanna M. Biernacka, Mark Frye, Susan L. McElroy, Laura J. Scott, Eli A. Stahl, Mikael Landén, Marian L. Hamshere, Olav B. Smeland, Srdjan Djurovic, Arne E. Vaaler, Ole A. Andreassen, Bernhard T. Baune, Tracy Air, Martin Preisig, Rudolf Uher, Douglas F. Levinson, Myrna M. Weissman, James B. Potash, Jianxin Shi, James A. Knowles, Roy H. Perlis, Susanne Lucae, Dorret I. Boomsma, Brenda W.J. H. Penninx, Jouke-Jan Hottenga, Eco J.C. de Geus, Gonneke Willemsen, Yuri Milaneschi, Henning Tiemeier, Hans J. Grabe, Alexander Teumer, Sandra Van der Auwera, Uwe Völker, Steven P. Hamilton, Patrik K.E. Magnusson, Alexander Viktorin, Divya Mehta, Niamh Mullins, Mark J. Adams, Gerome Breen, Andrew M. McIntosh, Cathryn M. Lewis, David M. Hougaard, Merete Nordentoft, Ole Mors, Preben B. Mortensen, Thomas Werge, Thomas D. Als, Anders D. Børglum, Tracey L. Petryshen, Jordan W. Smoller, Jill M. Goldstein.Sex-Dependent Shared and Non-Shared Genetic Architecture, Across Mood and Psychotic Disorders.Biological Psychiatry, 2021; DOI:10.1016/j.biopsych.2021.02.972

Cite This Page:

Massachusetts General Hospital. "Large-scale genome analysis identifies differences by sex in major psychiatric disorders." ScienceDaily. ScienceDaily, 23 March 2021. /releases/2021/03/210323150726.htm>.
Massachusetts General Hospital. (2021, March 23). Large-scale genome analysis identifies differences by sex in major psychiatric disorders.ScienceDaily. Retrieved September 6, 2023 from www.koonmotors.com/releases/2021/03/210323150726.htm
Massachusetts General Hospital. "Large-scale genome analysis identifies differences by sex in major psychiatric disorders." ScienceDaily. www.koonmotors.com/releases/2021/03/210323150726.htm (accessed September 6, 2023).

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