Characterising the shared genetic determinants of bipolar disorder, schizophrenia and risk-taking

被引:11
|
作者
Hindley, Guy [1 ,2 ,3 ]
Bahrami, Shahram [1 ,2 ]
Steen, Nils Eiel [1 ,2 ]
O'Connell, Kevin S. [1 ,2 ]
Frei, Oleksandr [1 ,2 ,4 ]
Shadrin, Alexey [1 ,2 ]
Bettella, Francesco [1 ,2 ]
Rodevand, Linn [1 ,2 ]
Fan, Chun C. [5 ,6 ]
Dale, Anders M. [5 ,7 ,8 ,9 ]
Djurovic, Srdjan [10 ,11 ]
Smeland, Olav B. [1 ,2 ]
Andreassen, Ole A. [1 ,2 ]
机构
[1] Univ Oslo, Inst Clin Med, NORMENT, N-0407 Oslo, Norway
[2] Oslo Univ Hosp, Div Mental Hlth & Addict, N-0407 Oslo, Norway
[3] Kings Coll London, Psychosis Studies, Inst Psychiat Psychol & Neurosci, London, England
[4] Univ Oslo, Dept Informat, Ctr Bioinformat, N-0316 Oslo, Norway
[5] Oslo Univ Hosp, Dept Neurol, Div Clin Neurosci, Oslo, Norway
[6] Univ Calif San Diego, Multimodal Imaging Lab, La Jolla, CA 92093 USA
[7] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA
[8] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA
[9] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA
[10] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway
[11] Univ Bergen, Dept Clin Sci, NORMENT, Bergen, Norway
基金
美国国家卫生研究院; 欧洲研究理事会;
关键词
DECISION-MAKING; TRAIT IMPULSIVITY; SUBSTANCE USE; PREVALENCE; ASSOCIATION; AGGRESSION; BEHAVIOR; DISEASE; HEALTH;
D O I
10.1038/s41398-021-01576-4
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Increased risk-taking is a central component of bipolar disorder (BIP) and is implicated in schizophrenia (SCZ). Risky behaviours, including smoking and alcohol use, are overrepresented in both disorders and associated with poor health outcomes. Positive genetic correlations are reported but an improved understanding of the shared genetic architecture between risk phenotypes and psychiatric disorders may provide insights into underlying neurobiological mechanisms. We aimed to characterise the genetic overlap between risk phenotypes and SCZ, and BIP by estimating the total number of shared variants using the bivariate causal mixture model and identifying shared genomic loci using the conjunctional false discovery rate method. Summary statistics from genome wide association studies of SCZ, BIP, risk-taking and risky behaviours were acquired (n = 82,315-466,751). Genomic loci were functionally annotated using FUMA. Of 8.6-8.7 K variants predicted to influence BIP, 6.6 K and 7.4 K were predicted to influence risk-taking and risky behaviours, respectively. Similarly, of 10.2-10.3 K variants influencing SCZ, 9.6 and 8.8 K were predicted to influence risk-taking and risky behaviours, respectively. We identified 192 loci jointly associated with SCZ and risk phenotypes and 206 associated with BIP and risk phenotypes, of which 68 were common to both risk-taking and risky behaviours and 124 were novel to SCZ or BIP. Functional annotation implicated differential expression in multiple cortical and sub-cortical regions. In conclusion, we report extensive polygenic overlap between risk phenotypes and BIP and SCZ, identify specific loci contributing to this shared risk and highlight biologically plausible mechanisms that may underlie risk-taking in severe psychiatric disorders.
引用
收藏
页数:10
相关论文
共 50 条
  • [41] Shared gene expression alterations in schizophrenia and bipolar disorder
    Shao, Ling
    Vawter, Marquis P.
    BIOLOGICAL PSYCHIATRY, 2008, 64 (02) : 89 - 97
  • [42] Shared and Distinct Neurogenetic Mechanisms for Schizophrenia and Bipolar Disorder
    Meyer-Lindenberg, Andreas
    BIOLOGICAL PSYCHIATRY, 2009, 65 (08) : 99S - 99S
  • [43] Shared impairment in associative learning in schizophrenia and bipolar disorder
    Brambilla, Paolo
    Cerruti, Stefania
    Bellani, Marcella
    Perlini, Cinzia
    Ferro, Adele
    Marinelli, Veronica
    Giusto, Daniele
    Tomelleri, Luisa
    Rambaldelli, Gianluca
    Tansella, Michele
    Diwadkar, Vaibhav A.
    PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2011, 35 (04): : 1093 - 1099
  • [44] TEMPORAL ORIENTATION AND PERCEIVED CONTROL AS DETERMINANTS OF RISK-TAKING
    STRICKLAND, LH
    LEWICKI, RJ
    KATZ, AM
    JOURNAL OF EXPERIMENTAL SOCIAL PSYCHOLOGY, 1966, 2 (02) : 143 - 151
  • [45] Risk-taking in schizophrenia and controls with and without cannabis dependence
    Fischer, Bernard A.
    McMahon, Robert P.
    Kelly, Deanna L.
    Wehring, Heidi J.
    Meyer, Walter A.
    Feldman, Stephanie
    Carpenter, William T.
    Gorelick, David A.
    SCHIZOPHRENIA RESEARCH, 2015, 161 (2-3) : 471 - 477
  • [46] NAPG may not be a common risk gene shared by bipolar disorder and schizophrenia in Chinese population
    Li, Xing-Wang
    Liu, Bao-Cheng
    Wang, Yang
    Zhao, Qing-Zhu
    Shen, Qi
    Chen, Shi-Qing
    Ji, Jue
    Yang, Feng-Ping
    Gao, Ling-Han
    Xu, Yifeng
    Feng, Guo-yin
    He, Lin
    He, Guang
    PSYCHIATRIC GENETICS, 2012, 22 (02) : 107 - 108
  • [47] Determinants of CEO strategic risk-taking in the airline industry
    Lee, Won Seok
    Moon, Joonho
    TOURISM MANAGEMENT PERSPECTIVES, 2016, 18 : 111 - 117
  • [48] Shared genetic risks of bipolar disorder and ADHD
    Kang, Seema
    LANCET PSYCHIATRY, 2016, 3 (12): : 1106 - 1106
  • [49] Creativity and Bipolar Disorder: A Shared Genetic Vulnerability
    Greenwood, Tiffany A.
    ANNUAL REVIEW OF CLINICAL PSYCHOLOGY, VOL 16, 2020, 2020, 16 : 239 - 264
  • [50] Shared genetic factors influence risk for bipolar disorder and alcohol use disorders
    Carmiol, N.
    Peralta, J. M.
    Almasy, L.
    Contreras, J.
    Pacheco, A.
    Escamilla, M. A.
    Knowles, E. E. M.
    Raventos, H.
    Glahn, D. C.
    EUROPEAN PSYCHIATRY, 2014, 29 (05) : 282 - 287