Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence
Jen-Chyong Wang,Richard A. Grucza,Carlos Cruchaga,Anthony L. Hinrichs,Sarah Bertelsen,John P. Budde,Louis Fox,E Goldstein,Oliver Reyes,Nancy L. Saccone,Scott F. Saccone,Xiaoling Xuei,K. K. Bucholz,Samuel Kuperman,Jr Ji Nurnberger,John P. Rice,Marc A. Schuckit,Jay A. Tischfield,Victor Hesselbrock,Bernice Porjesz,Howard J. Edenberg,Laura J. Bierut,Alison Goate +22 more
Reads0
Chats0
TLDR
It is observed that a different group of polymorphisms, spanning CHRNA5-CHRNA3, demonstrate association with alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) criteria.Abstract:
Alcohol dependence frequently co-occurs with cigarette smoking, another common addictive behavior. Evidence from genetic studies demonstrates that alcohol dependence and smoking cluster in families and have shared genetic vulnerability. Recently a candidate gene study in nicotine dependent cases and nondependent smoking controls reported strong associations between a missense mutation (rs16969968) in exon 5 of the CHRNA5 gene and a variant in the 3'-UTR of the CHRNA3 gene and nicotine dependence. In this study we performed a comprehensive association analysis of the CHRNA5-CHRNA3-CHRNB4 gene cluster in the Collaborative Study on the Genetics of Alcoholism (COGA) families to investigate the role of genetic variants in risk for alcohol dependence. Using the family-based association test, we observed that a different group of polymorphisms, spanning CHRNA5-CHRNA3, demonstrate association with alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) criteria. Using logistic regression we replicated this finding in an independent case-control series from the family study of cocaine dependence. These variants show low linkage disequilibrium with the SNPs previously reported to be associated with nicotine dependence and therefore represent an independent observation. Functional studies in human brain reveal that the variants associated with alcohol dependence are also associated with altered steady-state levels of CHRNA5 mRNA.read more
Citations
More filters
Journal ArticleDOI
Meta-analysis and imputation refines the association of 15q25 with smoking quantity
Jason Z. Liu,Federica Tozzi,Dawn M. Waterworth,Sreekumar G. Pillai,Pierandrea Muglia,Lefkos T. Middleton,Wade H. Berrettini,Christopher W. Knouff,Xin Yuan,Gérard Waeber,Peter Vollenweider,Martin Preisig,Nicholas J. Wareham,Jing Hua Zhao,Ruth J. F. Loos,Ins Barroso,Kay-Tee Khaw,Scott M. Grundy,Philip J. Barter,Robert W. Mahley,Antero Kesäniemi,Ruth McPherson,John B. Vincent,John Strauss,James L. Kennedy,Anne Farmer,Peter McGuffin,Richard O. Day,Keith Matthews,Per Bakke,Amund Gulsvik,Susanne Lucae,Marcus Ising,T. Brueckl,S. Horstmann,H.-Erich Wichmann,Rajesh Rawal,Norbert Dahmen,Claudia Lamina,Ozren Polasek,Lina Zgaga,Jennifer E. Huffman,Susan Campbell,Jaspal S. Kooner,John C. Chambers,Mary Susan Burnett,Joseph M. Devaney,Augusto D. Pichard,Kenneth M. Kent,Lowell F. Satler,Joseph M. Lindsay,Ron Waksman,Stephen E. Epstein,James F. Wilson,Sarah H. Wild,Harry Campbell,Veronique Vitart,Muredach P. Reilly,Mingyao Li,Liming Qu,Robert L. Wilensky,William H. Matthai,Hakon Hakonarson,Daniel J. Rader,Andre Franke,Michael Wittig,Arne Schäfer,Manuela Uda,Antonio Terracciano,Xiangjun Xiao,Fabio Busonero,Paul Scheet,David Schlessinger,David St Clair,Dan Rujescu,Gonçalo R. Abecasis,Hans J. Grabe,Alexander Teumer,Henry Völzke,Astrid Petersmann,Ulrich John,Igor Rudan,Igor Rudan,Caroline Hayward,Alan F. Wright,Ivana Kolcic,Benjamin J. Wright,John R. Thompson,Anthony J. Balmforth,Alistair S. Hall,Nilesh J. Samani,Carl A. Anderson,Tariq Ahmad,Christopher G. Mathew,Miles Parkes,Jack Satsangi,Mark J. Caulfield,Patricia B. Munroe,Martin Farrall,Anna F. Dominiczak,Jane Worthington,Wendy Thomson,Steve Eyre,Anne Barton,Vincent Mooser,Clyde Francks,Clyde Francks,Jonathan Marchini +107 more
TL;DR: The Oxford-GlaxoSmithKline study (Ox-GSK) as discussed by the authors performed a genome-wide meta-analysis of SNP association with smoking-related behavioral traits and found an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19) that includes CHRNA5, CHRNA3 and CHRNB4.
Journal ArticleDOI
Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD
Nancy L. Saccone,Nancy L. Saccone,Robert Culverhouse,Tae-Hwi Schwantes-An,Dale S. Cannon,Xiangning Chen,Sven Cichon,Ina Giegling,Shizhong Han,Younghun Han,Kaisu Keskitalo-Vuokko,Xiangyang Kong,Maria Teresa Landi,Jennie Z. Ma,Susan E. Short,Susan E. Short,Sarah H. Stephens,Victoria L. Stevens,Lingwei Sun,Yufei Wang,Angela S. Wenzlaff,Steven H. Aggen,Naomi Breslau,Peter Broderick,Nilanjan Chatterjee,Jingchun Chen,Andrew C. Heath,Markku Heliövaara,Nicole R. Hoft,David J. Hunter,Majken K. Jensen,Nicholas G. Martin,Grant W. Montgomery,Tianhua Niu,Thomas J. Payne,Leena Peltonen,Michele L. Pergadia,John P. Rice,Richard Sherva,Margaret R. Spitz,Juzhong Sun,Jen C. Wang,Robert B. Weiss,William Wheeler,Stephanie H. Witt,Bao-Zhu Yang,Neil E. Caporaso,Marissa A. Ehringer,Tim Eisen,Susan M. Gapstur,Joel Gelernter,Richard S. Houlston,Jaakko Kaprio,Jaakko Kaprio,Kenneth S. Kendler,Peter Kraft,Mark Leppert,Ming D. Li,Pamela A. F. Madden,Markus M. Nöthen,Sreekumar G. Pillai,Marcella Rietschel,Dan Rujescu,Ann G. Schwartz,Christopher I. Amos,Laura J. Bierut +65 more
TL;DR: This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior, and is the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance.
Journal ArticleDOI
Genome-wide association study of alcohol dependence implicates a region on chromosome 11
Howard J. Edenberg,Daniel L. Koller,Xiaoling Xuei,Leah Wetherill,Jeanette N. McClintick,Laura Almasy,Laura J. Bierut,Kathleen K. Bucholz,Alison Goate,Fazil Aliev,Danielle M. Dick,Victor Hesselbrock,Anthony L. Hinrichs,John Kramer,Samuel Kuperman,John I. Nurnberger,John P. Rice,Marc A. Schuckit,Robert E. Taylor,B. Todd Webb,Jay A. Tischfield,Bernice Porjesz,Tatiana Foroud +22 more
TL;DR: Combining evidence from the case-control study, the follow-up in families, and gene expression provided strongest support for the association of a cluster of genes on chromosome 11 with alcohol dependence.
Journal ArticleDOI
The CHRNA5-CHRNA3-CHRNB4 Nicotinic Receptor Subunit Gene Cluster Affects Risk for Nicotine Dependence in African-Americans and in European-Americans
Nancy L. Saccone,Jen C. Wang,Naomi Breslau,Eric O. Johnson,Dorothy K. Hatsukami,Scott F. Saccone,Richard A. Grucza,Lingwei Sun,Weimin Duan,John P. Budde,Robert Culverhouse,Louis Fox,Anthony L. Hinrichs,Joseph H. Steinbach,Meng Wu,John P. Rice,Alison Goate,Laura J. Bierut +17 more
TL;DR: It is shown that multiple variants in this gene cluster contribute to nicotine dependence risk, and some are also associated with functional effects on CHRNA5.
Journal ArticleDOI
New insights into the genetics of addiction
Ming D. Li,Margit Burmeister +1 more
TL;DR: This work aims to replicate genome-wide linkage and association studies that implicated several regions and genes in addiction to various substances, including alcohol and, more recently, tobacco, and to determine the functional mechanisms of these genes and variants.
References
More filters
Book
Applied Logistic Regression
David W. Hosmer,Stanley Lemeshow +1 more
TL;DR: Hosmer and Lemeshow as discussed by the authors provide an accessible introduction to the logistic regression model while incorporating advances of the last decade, including a variety of software packages for the analysis of data sets.
Journal ArticleDOI
Applied Logistic Regression.
TL;DR: Applied Logistic Regression, Third Edition provides an easily accessible introduction to the logistic regression model and highlights the power of this model by examining the relationship between a dichotomous outcome and a set of covariables.
Journal ArticleDOI
Haploview: analysis and visualization of LD and haplotype maps
TL;DR: Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface.
Journal ArticleDOI
A direct approach to false discovery rates
TL;DR: The calculation of the q‐value is discussed, the pFDR analogue of the p‐value, which eliminates the need to set the error rate beforehand as is traditionally done, and can yield an increase of over eight times in power compared with the Benjamini–Hochberg FDR method.
Related Papers (5)
Variants in nicotinic receptors and risk for nicotine dependence
Laura J. Bierut,Jerry A. Stitzel,Jen C. Wang,Anthony L. Hinrichs,Richard A. Grucza,Xiaoling Xuei,Nancy L. Saccone,Scott F. Saccone,Sarah Bertelsen,Louis Fox,William J. Horton,Naomi Breslau,John P. Budde,C. Robert Cloninger,Danielle M. Dick,Tatiana Foroud,Dorothy K. Hatsukami,Victor Hesselbrock,Eric O. Johnson,John Kramer,Samuel Kuperman,Pamela A. F. Madden,Kevin Mayo,John I. Nurnberger,Ovide F. Pomerleau,Bernice Porjesz,Oliver Reyes,Marc A. Schuckit,Gary E. Swan,Jay A. Tischfield,Howard J. Edenberg,John P. Rice,Alison Goate +32 more
Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs
Scott F. Saccone,Anthony L. Hinrichs,Nancy L. Saccone,Gary A. Chase,Karel Konvicka,Pamela A. F. Madden,Naomi Breslau,Eric O. Johnson,Dorothy K. Hatsukami,Ovide F. Pomerleau,Gary E. Swan,Alison Goate,Joni L. Rutter,Sarah Bertelsen,Louis Fox,Douglas A. Fugman,Nicholas G. Martin,Grant W. Montgomery,Jen C. Wang,Dennis G. Ballinger,John P. Rice,Laura J. Bierut +21 more
A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.
Thorgeir E. Thorgeirsson,Frank Geller,Patrick Sulem,Thorunn Rafnar,Anna Wiste,Anna Wiste,Kristinn P. Magnusson,Andrei Manolescu,Gudmar Thorleifsson,Hreinn Stefansson,Andres Ingason,Simon N. Stacey,Jon Thor Bergthorsson,Steinunn Thorlacius,Julius Gudmundsson,Thorlakur Jonsson,Margret Jakobsdottir,Jona Saemundsdottir,Olof Birna Olafsdottir,Larus J. Gudmundsson,Gyda Bjornsdottir,Kristleifur Kristjansson,Halla Skuladottir,Helgi J Isaksson,Tomas Gudbjartsson,Gregory T. Jones,Thomas Mueller,Anders Gottsäter,Andrea Flex,Katja K.H. Aben,Femmie de Vegt,Peter F.A. Mulders,Dolores Isla,Maria Vidal,Laura Asín,Berta Saez,L. Murillo,Thorsteinn Blondal,Halldor Kolbeinsson,Jón G. Stefánsson,Ingunn Hansdottir,Valgerdur Runarsdottir,Roberto Pola,Bengt Lindblad,Andre M. van Rij,Benjamin Dieplinger,Meinhard Haltmayer,Jose I. Mayordomo,Lambertus A. Kiemeney,Stefan E Matthiasson,Hogni Oskarsson,Thorarinn Tyrfingsson,Daniel F. Gudbjartsson,Jeffrey R. Gulcher,Steinn Jonsson,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Augustine Kong,Kari Stefansson,Kari Stefansson +59 more
Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1
Christopher I. Amos,Xifeng Wu,Peter Broderick,Ivan P. Gorlov,Jian Gu,Timothy Eisen,Qiong Dong,Qing Zhang,Xiangjun Gu,Jayaram Vijayakrishnan,Kate Sullivan,Athena Matakidou,Yufei Wang,Gordon B. Mills,Kimberly F. Doheny,Ya Yu Tsai,Wei Vivien Chen,Sanjay Shete,Margaret R. Spitz,Richard S. Houlston +19 more
A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
Rayjean J. Hung,James McKay,Valerie Gaborieau,Paolo Boffetta,Mia Hashibe,David Zaridze,Anush Mukeria,Neonilia Szeszenia-Dabrowska,Jolanta Lissowska,Peter Rudnai,Eleonora Fabianova,Dana Mates,Vladimir Bencko,Lenka Foretova,Vladimir Janout,Chu Chen,Gary E. Goodman,John K. Field,Triantafillos Liloglou,George Xinarianos,Adrian Cassidy,John R. McLaughlin,Geoffrey Liu,Steven A. Narod,Hans E. Krokan,Frank Skorpen,Maiken Bratt Elvestad,Kristian Hveem,Lars J. Vatten,Jakob Linseisen,Françoise Clavel-Chapelon,Paolo Vineis,H. Bas Bueno-de-Mesquita,Eiliv Lund,Carmen Martinez,Sheila Bingham,Torgny Rasmuson,Pierre Hainaut,Elio Riboli,Wolfgang Ahrens,Simone Benhamou,Pagona Lagiou,Dimitrios Trichopoulos,Ivana Holcatova,Franco Merletti,Kristina Kjærheim,Antonio Agudo,Gary J. Macfarlane,Renato Talamini,Lorenzo Simonato,Ray Lowry,David I. Conway,Ariana Znaor,Claire M. Healy,Diana Zelenika,Anne Boland,Marc Delepine,Mario Foglio,Doris Lechner,Fumihiko Matsuda,Hélène Blanché,Ivo Gut,Simon Heath,Mark Lathrop,Paul Brennan +64 more