Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

Autor: Michael Boehnke, Anke R. Hammerschlag, Stavroula Kanoni, Nilesh J. Samani, Stefan Blankenberg, Arpana Agrawal, Ersin Yavas, Chris Hsu, Dominique Arveiler, Giovanni Veronesi, Sarah E. Harris, Guillaume Lettre, Leah Wetherill, Helen R. Warren, M Samuel, Manav Kapoor, Praveen Surendran, Mengzhen Liu, Massimo Mangino, Abdulla Al Shafi Majumder, Chiara Batini, Jeff Haessler, Anton J. M. De Craen, Matt McGue, Laura J. Bierut, Yi Ling Chou, Markku Laakso, Ian J. Deary, Rebecca Rohde, Nhung Le, David Schlessinger, J. Dylan Weissenkampen, Claudia Langenberg, Tim D. Spector, Paul W. Franks, John P. Rice, Philippe M. Frossard, Hanieh Yaghootkar, Janie Corley, Frank Kee, J. Wouter Jukema, Pim van der Harst, Dermot F. Reily, Jenny Chang-Claude, Nicholas G. Martin, Tatiana Foroud, Sune F. Nielsen, Charles Kooperberg, Rudolf A. de Boer, Francesco Cucca, Paul D.P. Pharoah, Alex P. Reiner, Daniel R. Barnes, Anders Mälarstig, Jonathan Marten, Henry Völzke, Yu Jiang, Jukka Kontto, J Danesh, Antonis C. Antoniou, Andrew C. Heath, Nicholas J. Wareham, Joanna M. M. Howson, Alison Goate, Olov Rolandsson, Frida Renström, Chu Chen, Vinicius Tragante, Matt J. Neville, Kathleen Stirrups, Clemens Baumbach, Colin N. A. Palmer, Adam S. Butterworth, William G. Iacono, Naveed Sattar, Ian P. Hall, Daniel O. Stram, Giorgio Pistis, Jan-Håkan Jansson, Jaakko Kaprio, David R. Weir, David P. Strachan, Martin D. Tobin, Folkert W. Asselbergs, John M. Starr, Stefan Weiss, Thomas F. Vogt, Riccardo E. Marioni, Maarten Hoek, Jessica Tyrrell, Hilary A. Tindle, Alison M. Dunning, Anu Loukola, Joe Dennis, Victoria E. Jackson, Louise V. Wain, Eleftheria Zeggini, Weihua Zhang, Yaming Shao, Kari Kuulasmaa, Elisabeth Altmaier, Jean-Claude Tardif, Jian Gong, A. Mesut Erzurumluoglu, Andries R. van der Leij, Kari E. North, Anna F. Dominiczak, Martina Müller-Nurasyid, Scott I. Vrieze, Sarah Bertelsen, Markus Perola, Evangelos Evangelou, Chris J. Packard, Gonçalo R. Abecasis, Robert A. Scott, S. Trompet, Jennifer A. Smith, H. Steven Scholte, Timothy M. Frayling, Danielle Posthuma, Ian Ford, Douglas F. Easton, Børge Grønne Nordestgaard, Michiel L. Bots, Charles B. Eaton, Sharon L.R. Kardia, Dewan S. Alam, Xiaowei Zhan, Sean P. David, Maria Uria-Nickelsen, Dongbing Lai, Ilonca Vaartjes, Mark J. Caulfield, Valérie Turcot, Jean Ferrières, Emanuele Di Angelantonio, Robin Young, Pamela A. F. Madden, Tibor V. Varga, Asif Rasheed, Peter van der Meer, Dajiang J. Liu, Ioanna Tachmazidou, Panos Deloukas, Danish Saleheen, Evelin Mihailov, Caroline Hayward, Patricia B. Munroe, Beenish Qaiser, Jessica D. Faul, John C. Chambers, Matthias Nauck, Niek Verweij, Jordan M. Hughey, Christopher A. Haiman, Hans J. Grabe, Muriel Caslake, Saima Afaq, Jaspal S. Kooner, Tinca J. C. Polderman, Philippe Amouyel, Wei Zhao, Göran Hallmans, Andres Metspalu, Jarmo Virtamo, Carl A. Melbourne, Kaixin Zhou, Christiaan de Leeuw, Peter S. Sever, Eirini Marouli, Neil Poulter, Rajiv Chowdhury, Jian'an Luan, Deborah J. Thompson, F Karpe, Kyriaki Michailidou, David M. Brazel, Heather M. Stringham
Přispěvatelé: Brein en Cognitie (Psychologie, FMG), Psychology Other Research (FMG), Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Graduate School, Experimental Vascular Medicine, ACS - Diabetes & metabolism, Amsterdam Cardiovascular Sciences, ACS - Atherosclerosis & ischemic syndromes, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Laboratory Genetic Metabolic Diseases, Gastroenterology and Hepatology, Experimental Immunology, Radiotherapy, Cardiology, HUSLAB, Institute for Molecular Medicine Finland, Department of Public Health, Genetic Epidemiology, Barnes, Daniel [0000-0002-3781-7570], Erzurumluoglu, Mesut [0000-0003-1322-8138], Apollo - University of Cambridge Repository, Biological Psychology, Complex Trait Genetics
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Nonsynonymous substitution
Genome-wide association study
3124 Neurology and psychiatry
0302 clinical medicine
DEPENDENCE
Genotype
Databases
Genetic
SEQUENCE VARIANTS
GWAS
Exome
Non-U.S. Gov't
Oligonucleotide Array Sequence Analysis
Genetics
RISK
HERITABILITY
Research Support
Non-U.S. Gov't
Smoking
ASSOCIATION
3. Good health
ADH1B
Phenotype
Behavioral genetics
LOW-FREQUENCY
Alcohol
Heritability
Nicotine
Tobacco
Alcohol Drinking
Non-P.H.S
Single-nucleotide polymorphism
Biology
Research Support
Polymorphism
Single Nucleotide
N.I.H
03 medical and health sciences
Research Support
N.I.H.
Extramural
SDG 3 - Good Health and Well-being
Genetic variation
Journal Article
Humans
Genetic Predisposition to Disease
COMMON
Biological Psychiatry
3112 Neurosciences
Genetic Variation
Extramural
MISSENSE VARIANTS
R1
Genetic architecture
030104 developmental biology
U.S. Gov't
030217 neurology & neurosurgery
Research Support
U.S. Gov't
Non-P.H.S
Genome-Wide Association Study
Zdroj: Biological Psychiatry, 85(11), 946-955. Elsevier
Biological Psychiatry, 85(11), 946-955. Elsevier USA
Biological Psychiatry, 85(11), 946-955. ELSEVIER SCIENCE INC
Brazel, D M, Jiang, Y, Hughey, J M, Turcot, V, Zhan, X, Gong, J, Batini, C, Weissenkampen, J D, Liu, M, Barnes, D R, Bertelsen, S, Chou, Y-L, Erzurumluoglu, A M, Faul, J D, Haessler, J, Hammerschlag, A R, Hsu, C, Kapoor, M, Lai, D, Le, N, de Leeuw, C A, Loukola, A, Mangino, M, Melbourne, C A, Pistis, G, Qaiser, B, Rohde, R, Shao, Y, Stringham, H, Wetherill, L, Zhao, W, Agrawal, A, Bierut, L, Chen, C, Eaton, C B, Goate, A, Haiman, C, Heath, A, Iacono, W G, Martin, N G, Polderman, T J, Reiner, A, Rice, J, Schlessinger, D, Scholte, H S, Smith, J A, Tardif, J-C, Tindle, H A, van der Leij, A R, Boehnke, M, Chang-Claude, J, Cucca, F, David, S P, Foroud, T, Howson, J M M, Kardia, S L R, Kooperberg, C, Laakso, M, Lettre, G, Madden, P, Mcgue, M, North, K, Posthuma, D, Spector, T, Stram, D, Tobin, M D, Weir, D R, Kaprio, J, Abecasis, G R, Liu, D J, Vrieze, S, Surendran, P, Young, R, Barnes, D R, Nielsen, S F, Rasheed, A, Samuel, M, Zhao, W, Kontto, J, Perola, M, Caslake, M, de Craen, A J M, Trompet, S, Uria-Nickelsen, M, Malarstig, A, Reily, D F, Hoek, M, Vogt, T, Jukema, J W, Sattar, N, Ford, I, Packard, C J, Alam, D S, Majumder, A A S, Di Ange-Lantonio, E, Chowdhury, R, Amouyel, P, Arveiler, D, Blankenberg, S, Ferrieres, J, Kee, F, Kuulasmaa, K, Mueller-Nurasyid, M, Veronesi, G, Virtamo, J, Frossard, P, Nordestgaard, B G, Saleheen, D, Danesh, J, Butterworth, A S, Howson, J M M, Erzurumluoglu, A M, Jackson, V E, Melbourne, C A, Varga, T V, Warren, H R, Tragante, V, Tachmazidou, I, Harris, S E, Evangelou, E, Marten, J, Zhang, W, Altmaier, E, Luan, J, Langenberg, C, Scott, R A, Yaghootkar, H, Stirrups, K, Kanoni, S, Marouli, E, Karpe, F, Dominiczak, A F, Sever, P, Poulter, N, Rolandsson, O, Baumbach, C, Afaq, S, Chambers, J C, Kooner, J S, Wareham, N J, Renstrom, F, Hallmans, G, Marioni, R E, Corley, J, Starr, J M, Verweij, N, de Boer, R A, van der Meer, P, Yavas, E, Vaartjes, I, Bots, M L, Asselbergs, F W, Grabe, H J, Volzke, H, Nauck, M, Weiss, S, Pharoah, P D P, Dunning, A M, Dennis, J G, Thompson, D J, Michailidou, K, Easton, D F, Antoniou, A C, Tyrrell, J, Mihailov, E, Samani, N J, Zhou, K, Neville, M J, Metspalu, A, Palmer, C N A, Hall, I P, Strachan, D P, Deary, I J, Frayling, T M, Hayward, C, van der Harst, P, Zeggini, E, Munroe, P B, Jansson, J-H, Franks, P W, Deloukas, P, Caulfield, M J, Wain, L V & Tobin, M D 2019, ' Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use ', Biological Psychiatry, vol. 85, no. 11, pp. 946-955 . https://doi.org/10.1016/j.biopsych.2018.11.024
Biological Psychiatry, 85(11), 946. Elsevier USA
Brazel, D M, Jiang, Y, Hughey, J M, Turcot, V, Zhan, X, Gong, J, Batini, C, Weissenkampen, J D, Liu, M, Surendran, P, Young, R, Barnes, D R, Nielsen, S F, Rasheed, A, Samuel, M, Zhao, W, Kontto, J, Perola, M, Caslake, M, de Craen, A J M, Trompet, S, Uria-Nickelsen, M, Malarstig, A, Reily, D F, Hoek, M, Vogt, T, Jukema, J W, Sattar, N, Ford, I, Packard, C J, Alam, D S, Majumder, A A S, di Angelantonio, E, Chowdhury, R, Amouyel, P, Arveiler, D, Blankenberg, S, Ferrières, J, Kee, F, Kuulasmaa, K, Müller-Nurasyid, M, Veronesi, G, Virtamo, J, EPIC-CVD Consortium, Frossard, P, Nordestgaard, B R G, Saleheen, D, Danesh, J, Hammerschlag, A R, Posthuma, D, Spector, T, Stram, D O, Tobin, M D, Weir, D R, Kaprio, J, Abecasis, G R, Liu, D J, Vrieze, S & CHD Exome+ Consortium 2019, ' Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use ', Biological Psychiatry, vol. 85, no. 11, pp. 946-955 . https://doi.org/10.1016/j.biopsych.2018.11.024
Biological psychiatry. Elsevier USA
CHD Exome+ Consortium & Consortium for Genetics of Smoking Behaviour 2019, ' Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use ', Biological Psychiatry, vol. 85, no. 11, pp. 946-955 . https://doi.org/10.1016/j.biopsych.2018.11.024
ISSN: 0006-3223
Popis: BackgroundSmoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk.MethodsWe analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci.ResultsMeta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals.ConclusionsRare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.
Databáze: OpenAIRE
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