Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.
Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.
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DOI：
10.1038/s41380-019-0558-2
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发表时间：
2021-04
影响因子：
11
通讯作者：
Rietschel M
中科院分区：
文献类型：
--
作者：
Andlauer TFM;Guzman-Parra J;Streit F;Strohmaier J;González MJ;Gil Flores S;Cabaleiro Fabeiro FJ;Del Río Noriega F;Perez FP;Haro González J;Orozco Diaz G;de Diego-Otero Y;Moreno-Küstner B;Auburger G;Degenhardt F;Heilmann-Heimbach S;Herms S;Hoffmann P;Frank J;Foo JC;Treutlein J;Witt SH;Cichon S;Kogevinas M;Bipolar Disorder Working Group of the Psychiatric Genomics Consortium;Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium;Rivas F;Mayoral F;Müller-Myhsok B;Forstner AJ;Nöthen MM;Rietschel M
经常检查精神疾病患病率高的多重家族，以确定具有大效应量的罕见遗传变异。在本研究中，我们分析了双相情感障碍（BD）的风险在BD多发性家庭是否是由共同的遗传变异的影响。此外，我们调查了这种风险是否主要由BD特异性风险变体或与精神分裂症或重性抑郁症易感性相关的变体赋予。总共分析了来自33个安达卢西亚BD多重家族的395名个体（166名BD，78名重度抑郁症，151名未受影响）以及来自独立BD病例/对照队列的438名受试者（161名无关BD，277名无关对照）。计算BD、精神分裂症（SCZ）和重度抑郁症的多基因风险评分（PRS），并在队列间进行比较。家族性BD病例和未受影响的家庭成员对所有三种精神疾病的PRS均高于独立对照组，BD和SCZ在校正多重测试后具有显著性，表明家族中几种精神疾病的基线风险较高。此外，家族性BD病例的BD PRS显著高于未受影响的家庭成员和无关的BD病例。一个合理的假设是，在精神疾病风险普遍增加的多重家族中，BD的发展可归因于赋予BD特定风险的常见变异的高负担。目前的分析表明，常见的遗传风险变异的精神障碍可能有助于情感性精神障碍的高发病在多重家庭。然而，PRS仅解释了观察到的表型变异的一部分，罕见的变异也可能导致疾病的发展。
Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.
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影响因子：
3.7
作者：
Belonogova NM;Svishcheva GR;van Duijn CM;Aulchenko YS;Axenovich TI
通讯作者：
Axenovich TI
影响因子：
3.7
作者：
Forstner AJ;Hecker J;Hofmann A;Maaser A;Reinbold CS;Mühleisen TW;Leber M;Strohmaier J;Degenhardt F;Treutlein J;Mattheisen M;Schumacher J;Streit F;Meier S;Herms S;Hoffmann P;Lacour A;Witt SH;Reif A;Müller-Myhsok B;Lucae S;Maier W;Schwarz M;Vedder H;Kammerer-Ciernioch J;Pfennig A;Bauer M;Hautzinger M;Moebus S;Schenk LM;Fischer SB;Sivalingam S;Czerski PM;Hauser J;Lissowska J;Szeszenia-Dabrowska N;Brennan P;McKay JD;Wright A;Mitchell PB;Fullerton JM;Schofield PR;Montgomery GW;Medland SE;Gordon SD;Martin NG;Krasnov V;Chuchalin A;Babadjanova G;Pantelejeva G;Abramova LI;Tiganov AS;Polonikov A;Khusnutdinova E;Alda M;Cruceanu C;Rouleau GA;Turecki G;Laprise C;Rivas F;Mayoral F;Kogevinas M;Grigoroiu-Serbanescu M;Becker T;Schulze TG;Rietschel M;Cichon S;Fier H;Nöthen MM
通讯作者：
Nöthen MM
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
9.8
作者：
Cichon, Sven;Muehleisen, Thomas W.;Noethen, Markus M.
通讯作者：
Noethen, Markus M.