Genetic Relationship between Schizophrenia and Nicotine Dependence

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Chen , J , Bacanu , S A , Yu , H , Zhao , Z , Jia , P , Kendler , K S , Kranzler , H R , Gelernter , J , Farrer , L , Minica , C , Pool , R , Milaneschi , Y , Boomsma , D I , Penninx , B W , Tyndale , R F , Ware , J J , Vink , J M , Kaprio , J , Munafo , M , Chen , X , Ware , J J , Chen , X , Vink , J M , Loukola , A , Minica , C , Pool , R , Milaneschi , Y , Mangino , M , Menni , C , Chen , J , Peterson , R , Auro , K , Lyytikäinen , L-P , Wedenoja , J , Stiby , A I , Hemani , G , Willemsen , G , Hottenga , J J , Korhonen , T , Heliövaara , M , Perola , M , Rose , R , Paternoster , L , Timpson , N , Wassenaar , C A , Zhu , A Z , Smith , G D , Raitakari , O , Lehtimäki , T , Kähönen , M , Koskinen , S , Spector , T , Penninx , B W , Salomaa , V , Boomsma , D I , Tyndale , R F , Munafo , M , Ware , J J , Chen , X , Vink , J M , Minica , C , Chen , J , Peterson , R , Timpson , N , Taylor , M , Boomsma , D I , Munafo , M , Maes , H , Riley , B , Kendler , K S , Gelernter , J , Sherva , R , Farrer , L , Kranzler , H R , Maher , B & Vanyukov , M 2016 , ' Genetic Relationship between Schizophrenia and Nicotine Dependence ' , Scientific Reports , vol. 6 , 25671 , pp. 25671 . https://doi.org/10.1038/srep25671

Title: Genetic Relationship between Schizophrenia and Nicotine Dependence
Author: Chen, Jingchun; Bacanu, S. A.; Yu, H.; Zhao, Z.; Jia, P.; Kendler, K. S.; Kranzler, H. R.; Gelernter, J.; Farrer, L.; Minica, C.; Pool, R.; Milaneschi, Y.; Boomsma, D. I.; Penninx, B. W.; Tyndale, R. F.; Ware, J. J.; Vink, J. M.; Kaprio, Jaakko; Munafo, M.; Chen, X.; Ware, J. J.; Chen, X.; Vink, J. M.; Loukola, Anu; Minica, C.; Pool, R.; Milaneschi, Y.; Mangino, M.; Menni, C.; Chen, J.; Peterson, R.; Auro, Kirsi; Lyytikäinen, Leo-Pekka; Wedenoja, Juho; Stiby, A. I.; Hemani, G.; Willemsen, G.; Hottenga, J. J.; Korhonen, Tellervo; Heliövaara, Markku; Perola, Markus; Rose, R.; Paternoster, L.; Timpson, N.; Wassenaar, C. A.; Zhu, A. Z.; Smith, G. D.; Raitakari, Olli; Lehtimäki, Terho; Kähönen, Mika; Koskinen, Seppo; Spector, T.; Penninx, B. W.; Salomaa, Veikko; Boomsma, D. I.; Tyndale, R. F.; Munafo, M.; Ware, J. J.; Chen, X.; Vink, J. M.; Minica, C.; Chen, J.; Peterson, R.; Timpson, N.; Taylor, M.; Boomsma, D. I.; Munafo, M.; Maes, H.; Riley, B.; Kendler, K. S.; Gelernter, J.; Sherva, R.; Farrer, L.; Kranzler, H. R.; Maher, B.; Vanyukov, M.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Department of Public Health
University of Helsinki, National Institute for Health and Welfare (THL)
University of Helsinki, Department of Public Health
University of Helsinki, Department of Public Health
University of Helsinki, National Institute for Health and Welfare (THL)
Date: 2016-05-01
Language: eng
Number of pages: 10
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/163022
Abstract: It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerstrom test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 x 10(-3) and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 x 10(-3) and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity.
Subject: GENOME-WIDE ASSOCIATION
LONG-TERM POTENTIATION
RECEPTOR SUBUNIT GENE
FALSE DISCOVERY RATE
COMMON VARIANTS
BIPOLAR DISORDER
SMOKING-BEHAVIOR
TOBACCO SMOKING
RISK
SMOKERS
3111 Biomedicine
3142 Public health care science, environmental and occupational health
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