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Genetic Relationship between Schizophrenia and Nicotine Dependence

Scientific Reports2016Vol. 6(1), pp. 25671–25671

Citations Over TimeTop 10% of 2016 papers

Jingchun Chen, Silviu‐Alin Bacanu, Hui Yu, Zhongming Zhao, Peilin Jia, Kenneth S. Kendler, Henry R. Kranzler, Joel Gelernter, Lindsay A. Farrer, Camelia C. Minică, René Pool, Yuri Milaneschi, Dorret I. Boomsma, Brenda W.J.H. Penninx, Rachel F. Tyndale, Jennifer J. Ware, Jacqueline M. Vink, Jaakko Kaprio, Marcus Munafò, Xiangning Chen, Cotinine meta-analysis group, Jennifer J. Ware, Xiangning Chen, Jacqueline M. Vink, Anu Loukola, Camelia Minica, René Pool, Yuri Milaneschi, Massimo Mangino, Cristina Menni, Jingchun Chen, Roseann Peterson, Kirsi Auro, Leo‐Pekka Lyytikäinen, Juho Wedenoja, Alex I. Stiby, Gibran Hemani, Gonneke Willemsen, Jouke‐Jan Hottenga, Tellervo Korhonen, Markku Heliövaara, Markus Perola, Richard J. Rose, Lavinia Paternoster, Nicholas J. Timpson, Catherine A. Wassenaar, Andy Z. X. Zhu, George Davey Smith, Olli Raitakari, Terho Lehtimäki, Mika Kähönen, Seppo Koskinen, Timothy D. Spector, Brenda W. J. H. Penninx, Veikko Salomaa, Dorret I. Boomsma, Rachel F. Tyndale, Jaakko Kaprio, Marcus Munafò, FTND meta-analysis group, Jennifer J. Ware, Xiangning Chen, Jacqueline M. Vink, Anu Loukola, Camelia Minica, Jingchun Chen, Roseann Peterson, Nicholas J. Timpson, Michelle Taylor, Dorret I. Boomsma, Jaakko Kaprio, Marcus R. Munafò, Hermine H. Maes, Brien P. Riley, Kenneth S. Kendler, Joel Gelernter, Richard Sherva, Lindsay A. Farrer, Henry R. Kranzler, Brion S. Maher, Michael M. Vanyukov

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), Fagerström 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 × 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 × 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.

Citations Over TimeTop 10% of 2016 papers

Abstract

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