@article{b8b4bdf599114c779a7b78a5ad63e1a0,
title = "Identification of shared genetic variants between schizophrenia and lung cancer",
abstract = "Epidemiology studies suggest associations between schizophrenia and cancer. However, the underlying genetic mechanisms are not well understood, and difficult to identify from epidemiological data. We investigated if there is a shared genetic architecture between schizophrenia and cancer, with the aim to identify specific overlapping genetic loci. First, we performed genome-wide enrichment analysis and second, we analyzed specific loci jointly associated with schizophrenia and cancer by the conjunction false discovery rate. We analyzed the largest genome-wide association studies of schizophrenia and lung, breast, prostate, ovary, and colon-rectum cancer including more than 220,000 subjects, and included genetic association with smoking behavior. Polygenic enrichment of associations with lung cancer was observed in schizophrenia, and weak enrichment for the remaining cancer sites. After excluding the major histocompatibility complex region, we identified three independent loci jointly associated with schizophrenia and lung cancer. The strongest association included nicotinic acetylcholine receptors and is an established pleiotropic locus shared between lung cancer and smoking. The two other loci were independent of genetic association with smoking. Functional analysis identified downstream pleiotropic effects on epigenetics and gene-expression in lung and brain tissue. These findings suggest that genetic factors may explain partly the observed epidemiological association of lung cancer and schizophrenia.",
author = "Verena Zuber and J{\"o}nsson, {Erik G.} and Oleksandr Frei and Aree Witoelar and Thompson, {Wesley K.} and Schork, {Andrew J.} and Francesco Bettella and Yunpeng Wang and Srdjan Djurovic and Smeland, {Olav B.} and Ingrid Dieset and Fanous, {Ayman H.} and Desikan, {Rahul S.} and S{\'e}bastien K{\"u}ry and St{\'e}phane B{\'e}zieau and Dale, {Anders M.} and Mills, {Ian G.} and Andreassen, {Ole A.}",
note = "Funding Information: The work was supported by the Research Council of Norway, KG Jebsen Stiftelsen, and South East Norway Health Authority. The authors would like to thank the study participants and the members of the different consortia contributing summary statistics data. This work would not have been possible without the Psychiatric Genomics Consortium (PGC) Schizophrenia Work Groups, the Tobacco and Genetics (TAG) Consortium, and the Colon Cancer Family Registries (Colon CFR), and ColoRectal Transdisciplinary Study (CORECT) consortia, the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) consortium, the Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI) Research Team, the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) Consortium, Transdisciplinary Research in Cancer of the Lung (TRICL) Research Team. In particular, the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) breast cancer genome-wide association study meta-analysis was supported by U19 CA148065. The following genome-wide association studies and investigators that shared genome-wide summary data as part of the DRIVE meta-analysis: the Australian Breast Cancer Family Study (ABCFS) (John L Hopper, Melissa C. Southey, Enes Makalic, Daniel F. Schmidt), the British Breast Cancer Study (BBCS) (Olivia Fletcher, Julian Peto, Lorna Gibson, Isabel dos Santos Silva), the Breast and Prostate Cancer Cohort Consortium (BPC3) (David J. Hunter, Sara Lindstr{\"o}m, Peter Kraft), the Breast Cancer Family Registries (BCFR) (Habib Ahsan, Alice Whittemore), the Dutch Familial Bilateral Breast Cancer Study (DFBBCS) (Quinten Waisfisz, Hanne Meijers-Heijboer, Muriel Adank, Rob B van der Luijt, Andre G Uitterlinden, Albert Hofman), German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) (Alfons Meindl, Rita K. Schmutzler, Bertram M{\"u}ller-Myhsok, Peter Lichtner), the Helsinki breast cancer family Study (HEBCS) (Heli Nevanlinna, Taru A Muranen, Kristiina Aittom{\"a}ki, Carl Blomqvist), the Mammary Carcinoma Risk factor Investigation (MARIE) (Jenny Chang-Claude, Rebecca Hein, Norbert Dahmen, Lars Beckman), SardiNIA (Laura Crisponi), the Singapore and Sweden Breast Cancer Study (SASBAC) (Per Hall, Kamila Czene, Astrid Irwanto, Jianjun Liu), and the UK2 GWAS (Douglas F Easton, Clare Turnbull, Nazneen Rahman). Furthermore, the COGS study would not have been possible without the contributions of the following: Per Hall (COGS); Douglas F. Easton, Paul Pharoah, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang (BCAC), Andrew Berchuck (OCAC), Rosalind A. Eeles, Douglas F. Easton, Ali Amin Al Olama, Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL), Georgia Chenevix-Trench, Antonis Antoniou, Lesley McGuffog, Fergus Couch and Ken Offit (CIMBA), Joe Dennis, Alison M. Dunning, Andrew Lee, and Ed Dicks, Craig Luccarini and the staff of the Centre for Genetic Epidemiology Laboratory, Javier Benitez, Anna Gonzalez-Neira and the staff of the CNIO genotyping unit, Jacques Simard and Daniel C. Tessier, Francois Bacot, Daniel Vincent, Sylvie LaBoissi{\`e}re and Frederic Robidoux and the staff of the McGill University and G{\'e}nome Qu{\'e}bec Innovation Centre, Stig E. Bojesen, Sune F. Nielsen, Borge G. Nordestgaard, and the staff of the Copenhagen DNA laboratory, and Julie M. Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. Funding for the iCOGS infrastructure came from: the European Community{\textquoteright}s Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/ A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. A full list of consortium members appears in the Supplementary Information. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41598-017-16481-4",
language = "English (US)",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}