@article{b403adaf65944c4d837e5ab35c66f387,
title = "A Systematic Single Nucleotide Polymorphism Screen to Fine-Map Alcohol Dependence Genes on Chromosome 7 Identifies Association With a Novel Susceptibility Gene ACN9",
abstract = "Background: Chromosome 7 has shown consistent evidence of linkage with a variety of phenotypes related to alcohol dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) project. With a sample of 262 densely affected families, a peak logarithm of odds (LOD) score for alcohol dependence of 2.9 was observed at D7S1799. The LOD score in the region increased to 4.1 when a subset of the sample was genotyped with the Illumina Linkage III panel for the Genetic Analysis Workshop 14 (GAW14). To follow up on this linkage region, we systematically screened single nucleotide polymorphisms (SNPs) across a 2 LOD support interval surrounding the alcohol dependence peak. Methods: The SNPs were selected from the HapMap Phase I CEPH data to tag linkage disequilibrium bins across the region. Across the 18-Mb region, genotyped by the Center for Inherited Disease Research (CIDR), 1340 SNPs were analyzed. Family-based association analyses were performed on a sample of 1172 individuals from 217 Caucasian families. Results: Eight SNPs showed association with alcohol dependence at p < .01. Four of the eight most significant SNPs were located in or very near the ACN9 gene. We conducted additional genotyping across ACN9 and identified multiple variants with significant evidence of association with alcohol dependence. Conclusions: These analyses suggest that ACN9 is involved in the predisposition to alcohol dependence. Data from yeast suggest that ACN9 is involved in gluconeogenesis and the assimilation of ethanol or acetate into carbohydrate.",
keywords = "ACN9, alcohol dependence, association, genetics, linkage disequilibrium",
author = "Dick, {Danielle M.} and Fazil Aliev and Wang, {Jen C.} and Scott Saccone and Anthony Hinrichs and Sarah Bertelsen and John Budde and Nancy Saccone and Tatiana Foroud and John Nurnberger and Xiaoling Xuei and Conneally, {P. M.} and Marc Schuckit and Laura Almasy and Raymond Crowe and Samuel Kuperman and John Kramer and Tischfield, {Jay A.} and Victor Hesselbrock and Edenberg, {Howard J.} and Bernice Porjesz and Rice, {John P.} and Laura Bierut and Alison Goate",
note = "Funding Information: The Collaborative Study on the Genetics of Alcoholism (COGA) (Co-Principal Investigators: L. Bierut, H. Edenberg, V. Hesselbrock, B. Porjesz) includes nine different centers where data collection, analysis, and storage take place. The nine sites and Principal Investigators and Co-Investigators are: University of Connecticut (V. Hesselbrock); Indiana University (H. Edenberg, J. Nurnberger Jr., P.M. Conneally, T. Foroud); University of Iowa (S. Kuperman, R. Crowe); SUNY HSCB (B. Porjesz, H. Begleiter); Washington University in St. Louis (L. Bierut, A. Goate, J. Rice); University of California at San Diego (M. Schuckit); Howard University (R. Taylor); Rutgers University (J. Tischfield); and the Southwest Foundation (L. Almasy). Zhaoxia Ren serves as the NIAAA Staff Collaborator. This national collaborative study is supported by National Institutes of Health (NIH) Grant U10AA08401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). In memory of Henri Begleiter, Ph.D., and Theodore Reich, M.D., Principal and Co-Principal Investigators of COGA, we acknowledge their immeasurable and fundamental scientific contributions to COGA and the field. The author SS was supported by American Cancer Society grant IRG-58-010-50; NLS was supported by NIDA grant K01DA015129. Genotyping services were provided by CIDR. CIDR is fully funded through a federal contract from the NIH to The Johns Hopkins University, Contract Number N01-HG-65403. All authors were provided with the Biological Psychiatry guidelines from the web for Disclosure of Biomedical Financial Interests and Potential Conflicts of Interest. Dr. Raymond Crowe reported that he has consulted with a law firm that is defending the Pfizer company in lawsuits against its product Zoloft. All other authors reported no interests to disclose related to this report. ",
year = "2008",
month = jun,
day = "1",
doi = "10.1016/j.biopsych.2007.11.005",
language = "English",
volume = "63",
pages = "1047--1053",
journal = "Biological Psychiatry",
issn = "0006-3223",
number = "11",
}