The genetic relationship between female reproductive traits and six psychiatric disorders

被引:18
作者
Ni, Guiyan [1 ,2 ,3 ]
Amare, Azmeraw T. [4 ,5 ]
Zhou, Xuan [2 ]
Mills, Natalie [5 ]
Gratten, Jacob [1 ,6 ]
Lee, S. Hong [2 ]
机构
[1] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia
[2] Univ South Australia, Australian Ctr Precis Hlth, Canc Res Inst, Adelaide, SA 5000, Australia
[3] Univ New England, Sch Environm & Rural Sci, Armidale, NSW 2351, Australia
[4] SAHMRI, South Australian Acad Hlth Sci & Translat Ctr, Adelaide, SA, Australia
[5] Univ Adelaide, Sch Med, Discipline Psychiat, Adelaide, SA, Australia
[6] Univ Queensland, Mater Res Inst, Brisbane, Qld 4072, Australia
基金
澳大利亚研究理事会; 英国医学研究理事会;
关键词
BIPOLAR AFFECTIVE-DISORDER; GENOME-WIDE ASSOCIATION; MATERNAL AGE; MENDELIAN RANDOMIZATION; PARENTAL AGE; PATERNAL AGE; RISK; SCHIZOPHRENIA; CHILDHOOD; HEALTH;
D O I
10.1038/s41598-019-48403-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Female reproductive behaviours have important implications for evolutionary fitness and health of offspring. Here we used the second release of UK Biobank data (N = 220,685) to evaluate the association between five female reproductive traits and polygenic risk scores (PRS) projected from genome-wide association study summary statistics of six psychiatric disorders (N = 429,178). We found that the PRS of attention-deficit/hyperactivity disorder (ADHD) were strongly associated with age at first birth (AFB) (genetic correlation of -0.68 +/- 0.03), age at first sexual intercourse (AFS) (-0.56 +/- 0.03), number of live births (NLB) (0.36 +/- 0.04) and age at menopause (-0.27 +/- 0.04). There were also robustly significant associations between the PRS of eating disorder (ED) and AFB (0.35 +/- 0.06), ED and AFS (0.19 +/- 0.06), major depressive disorder (MDD) and AFB (-0.27 +/- 0.07), MDD and AFS (-0.27 +/- 0.03) and schizophrenia and AFS (-0.10 +/- 0.03). These associations were mostly explained by pleiotropic effects and there was little evidence of causal relationships. Our findings can potentially help improve reproductive health in women, hence better child outcomes. Our findings also lend partial support to the evolutionary hypothesis that causal mutations underlying psychiatric disorders have positive effects on reproductive success.
引用
收藏
页数:12
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共 61 条
[21]  
Demontis D., 2017, bioRxiv, DOI DOI 10.1101/145581
[22]   Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa [J].
Duncan, Laramie ;
Yilmaz, Zeynep ;
Gaspar, Helena ;
Walters, Raymond ;
Goldstein, Jackie ;
Anttila, Verneri ;
Bulik-Sullivan, Brendan ;
Ripke, Stephan ;
Thornton, Laura ;
Daly, Mark ;
Sullivan, Patrick F. ;
Zeggini, Eleftheria ;
Breen, Gerome ;
Bulik, Cynthia M. ;
Adan, Roger ;
Alfredsson, Lars ;
Ando, Tetsuya ;
Andreassen, Ole ;
Aschauer, Harald ;
Baker, Jessica ;
Barrett, Jeffrey ;
Bencko, Vladimir ;
Bergen, Andrew ;
Berrettini, Wade ;
Birgegard, Andreas ;
Boni, Claudette ;
Perica, Vesna Boraska ;
Brandt, Harry ;
Burghardt, Roland ;
Carlberg, Laura ;
Cassina, Matteo ;
Cesta, Carolyn ;
Cichon, Sven ;
Clementi, Maurizio ;
Cohen-Woods, Sarah ;
Coleman, Joni ;
Cone, Roger ;
Courtet, Philippe ;
Crawford, Steven ;
Crow, Scott ;
Crowley, Jim ;
Danner, Unna ;
Davis, Oliver ;
de Zwaan, Martina ;
Dedoussis, George ;
Degortes, Daniela ;
DeSocio, Janiece ;
Dick, Danielle ;
Dikeos, Dimitris ;
Dina, Christian .
AMERICAN JOURNAL OF PSYCHIATRY, 2017, 174 (09) :850-858
[23]   Using Evolutionary Theory to Guide Mental Health Research [J].
Durisko, Zachary ;
Mulsant, Benoit H. ;
McKenzie, Kwame ;
Andrews, Paul W. .
CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE, 2016, 61 (03) :159-165
[24]   Paternal and maternal age as risk factors for psychosis: findings from Denmark, Sweden and Australia [J].
El-Saadi, O ;
Pedersen, CB ;
McNeil, TF ;
Saha, S ;
Welham, J ;
O'Callaghan, E ;
Cantor-Graae, E ;
Chant, D ;
Mortensen, PB ;
McGrath, J .
SCHIZOPHRENIA RESEARCH, 2004, 67 (2-3) :227-236
[25]  
Escott-Price V, 2019, AM J PSYCHIAT
[26]   The association between cannabis abuse and subsequent schizophrenia: a Swedish national co-relative control study [J].
Giordano, G. N. ;
Ohlsson, H. ;
Sundquist, K. ;
Sundquist, J. ;
Kendler, K. S. .
PSYCHOLOGICAL MEDICINE, 2015, 45 (02) :407-414
[27]   Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations [J].
Gratten, Jacob ;
Wray, Naomi R. ;
Peyrot, Wouter J. ;
McGrath, John J. ;
Visscher, Peter M. ;
Goddard, Michael E. .
NATURE GENETICS, 2016, 48 (07) :718-+
[28]   Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption [J].
Hartwig, Fernando Pires ;
Smith, George Davey ;
Bowden, Jack .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2017, 46 (06) :1985-1998
[29]   The MR-Base platform supports systematic causal inference across the human phenome [J].
Hemani, Gibran ;
Zhengn, Jie ;
Elsworth, Benjamin ;
Wade, Kaitlin H. ;
Haberland, Valeriia ;
Baird, Denis ;
Laurin, Charles ;
Burgess, Stephen ;
Bowden, Jack ;
Langdon, Ryan ;
Tan, Vanessa Y. ;
Yarmolinsky, James ;
Shihab, Hashem A. ;
Timpson, Nicholas J. ;
Evans, David M. ;
Relton, Caroline ;
Martin, Richard M. ;
Smith, George Davey ;
Gaunt, Tom R. ;
Haycock, Philip C. .
ELIFE, 2018, 7
[30]   Parental age and the risk of autism spectrum disorders: findings from a Swedish population-based cohort [J].
Idring, Selma ;
Magnusson, Cecilia ;
Lundberg, Michael ;
Ek, Mats ;
Rai, Dheeraj ;
Svensson, Anna C. ;
Dalman, Christina ;
Karlsson, Hakan ;
Lee, Brian K. .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2014, 43 (01) :107-115