Медицинская библиотека · The American journal of psychiatry · 2019

GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores.

Mullins Niamh, Bigdeli Tim B, Børglum Anders D, Coleman Jonathan R I, Demontis Ditte, Mehta Divya, Power Robert A, Ripke Stephan, Stahl Eli A, Starnawska Anna, Anjorin Adebayo, M.R.C.Psych, Corvin Aiden, Sanders Alan R, Forstner Andreas J, Reif Andreas, Koller Anna C, Świątkowska Beata, Baune Bernhard T, Müller-Myhsok Bertram, Penninx Brenda W J H, Pato Carlos, Zai Clement, Rujescu Dan, Hougaard David M, Quested Digby, Levinson Douglas F, Binder Elisabeth B, Byrne Enda M, Agerbo Esben, Dr.Med.Sc, Streit Fabian, Mayoral Fermin, Bellivier Frank, Degenhardt Franziska, Breen Gerome, Morken Gunnar, Turecki Gustavo, Rouleau Guy A, Grabe Hans J, Völzke Henry, Jones Ian, Giegling Ina, Agartz Ingrid, Melle Ingrid, Lawrence Jacob, M.R.C.Psych, Walters James T R, Strohmaier Jana, Shi Jianxin, Hauser Joanna, Biernacka Joanna M, Vincent John B, Kelsoe John, Strauss John S, Lissowska Jolanta, Pimm Jonathan, M.R.C.Psych, Smoller Jordan W, Guzman-Parra José, Berger Klaus, Scott Laura J, Jones Lisa A, Azevedo M Helena, Trzaskowski Maciej, Kogevinas Manolis, Rietschel Marcella, Boks Marco, Ising Marcus, Grigoroiu-Serbanescu Maria, Hamshere Marian L, Leboyer Marion, Frye Mark, Nöthen Markus M, Alda Martin, Preisig Martin, Nordentoft Merete, Boehnke Michael, O'Donovan Michael C, Owen Michael J, Pato Michele T, Renteria Miguel E, Budde Monika, Dipl.-Psych, Weissman Myrna M, Wray Naomi R, Bass Nicholas, M.R.C.Psych, Craddock Nicholas, Smeland Olav B, Andreassen Ole A, Mors Ole, Gejman Pablo V, Sklar Pamela, McGrath Patrick, Hoffmann Per, McGuffin Peter, Lee Phil H, Mortensen Preben Bo, Kahn René S, Ophoff Roel A, Adolfsson Rolf, Van der Auwera Sandra, Djurovic Srdjan, Kloiber Stefan, Heilmann-Heimbach Stefanie, Jamain Stéphane, Hamilton Steven P, McElroy Susan L, Lucae Susanne, Cichon Sven, Schulze Thomas G, Hansen Thomas, Werge Thomas, Air Tracy M, Nimgaonkar Vishwajit, Appadurai Vivek, Cahn Wiepke, Milaneschi Yuri, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Fanous Ayman H, Kendler Kenneth S, McQuillin Andrew, Lewis Cathryn M

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Аннотация

OBJECTIVE

More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.

METHODS

The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.

RESULTS

Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).

CONCLUSIONS

This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.

Для цитирования: Mullins Niamh, Bigdeli Tim B, Børglum Anders D, Coleman Jonathan R I, Demontis Ditte, Mehta Divya, Power Robert A, Ripke Stephan, Stahl Eli A, Starnawska Anna, Anjorin Adebayo, M.R.C.Psych, Corvin Aiden, Sanders Alan R, Forstner Andreas J, Reif Andreas, Koller Anna C, Świątkowska Beata, Baune Bernhard T, Müller-Myhsok Bertram, Penninx Brenda W J H, Pato Carlos, Zai Clement, Rujescu Dan, Hougaard David M, Quested Digby, Levinson Douglas F, Binder Elisabeth B, Byrne Enda M, Agerbo Esben, Dr.Med.Sc, Streit Fabian, Mayoral Fermin, Bellivier Frank, Degenhardt Franziska, Breen Gerome, Morken Gunnar, Turecki Gustavo, Rouleau Guy A, Grabe Hans J, Völzke Henry, Jones Ian, Giegling Ina, Agartz Ingrid, Melle Ingrid, Lawrence Jacob, M.R.C.Psych, Walters James T R, Strohmaier Jana, Shi Jianxin, Hauser Joanna, Biernacka Joanna M, Vincent John B, Kelsoe John, Strauss John S, Lissowska Jolanta, Pimm Jonathan, M.R.C.Psych, Smoller Jordan W, Guzman-Parra José, Berger Klaus, Scott Laura J, Jones Lisa A, Azevedo M Helena, Trzaskowski Maciej, Kogevinas Manolis, Rietschel Marcella, Boks Marco, Ising Marcus, Grigoroiu-Serbanescu Maria, Hamshere Marian L, Leboyer Marion, Frye Mark, Nöthen Markus M, Alda Martin, Preisig Martin, Nordentoft Merete, Boehnke Michael, O'Donovan Michael C, Owen Michael J, Pato Michele T, Renteria Miguel E, Budde Monika, Dipl.-Psych, Weissman Myrna M, Wray Naomi R, Bass Nicholas, M.R.C.Psych, Craddock Nicholas, Smeland Olav B, Andreassen Ole A, Mors Ole, Gejman Pablo V, Sklar Pamela, McGrath Patrick, Hoffmann Per, McGuffin Peter, Lee Phil H, Mortensen Preben Bo, Kahn René S, Ophoff Roel A, Adolfsson Rolf, Van der Auwera Sandra, Djurovic Srdjan, Kloiber Stefan, Heilmann-Heimbach Stefanie, Jamain Stéphane, Hamilton Steven P, McElroy Susan L, Lucae Susanne, Cichon Sven, Schulze Thomas G, Hansen Thomas, Werge Thomas, Air Tracy M, Nimgaonkar Vishwajit, Appadurai Vivek, Cahn Wiepke, Milaneschi Yuri, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Fanous Ayman H, Kendler Kenneth S, McQuillin Andrew, Lewis Cathryn M. GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores.. The American journal of psychiatry. 2019. DOI: 10.1176/appi.ajp.2019.18080957.

Предметные рубрики MeSH

Bipolar Disorder Case-Control Studies Major Depressive Disorder Female Genome-Wide Association Study Humans Male Multifactorial Inheritance Risk Factors Schizophrenia Suicide, Attempted

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