@article{c364a6df9101435c843b33cbf0282c2c,
title = "A regulatory variation in OPRK1, the gene encoding the κ-opioid receptor, is associated with alcohol dependence",
abstract = "Variations in OPRK1, which encodes the κ-opioid receptor, are associated with the risk for alcohol dependence. Sequencing DNAs with higher and lower risk haplotypes revealed an insertion/deletion (indel) with a net addition of 830 bp located 1986 bp upstream of the translation start site (1389 bp upstream of the transcription start site). We demonstrated that the upstream region extending from -1647 to -10 bp or from -2312 to -10 bp (relative to the translation start site) could function as a promoter in transient transfection assays. We then determined that the presence of the indel reduced transcriptional activity by half. We used a PCR assay to genotype individuals in 219 multiplex alcohol-dependent families of European American descent for the presence or absence of this indel. Family-based association analyses detected significant evidence of association of this insertion with alcoholism; the longer allele (with the indel), which had lower expression, is associated with higher risk for alcoholism. This indel is, therefore, a functional regulatory variation likely to explain at least part of the association of OPRK1 with alcohol dependence.",
author = "Edenberg, {Howard J.} and Jun Wang and Huijun Tian and Sirisha Pochareddy and Xiaoling Xuei and Leah Wetherill and Alison Goate and Tony Hinrichs and Samuel Kuperman and Nurnberger, {John I.} and Marc Schuckit and Tischfield, {Jay A.} and Tatiana Foroud",
note = "Funding Information: The Collaborative Study on the Genetics of Alcoholism (COGA)—Co-Principal Investigators: B. Porjesz, V. Hesselbrock, H. Edenberg, L. Bierut—includes nine different centers where data collection, analysis and storage take place. The nine sites and Principal Investigators and CoInvestigators are University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr, T. Foroud); University of Iowa (S. Kuperman, R. Crowe); SUNY Downstate (B. Porjesz); 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); Southwest Foundation (L. Almasy). Zhaoxia Ren serves as the NIAAA Staff Collaborator. This work is in memory of Henri Begleiter and Theodore Reich, Principal and Co-Principal Investigators of COGA since its inception; we are indebted to their leadership in the establishment and nurturing of COGA and acknowledge with great admiration their seminal scientific contributions to the field. Funding to pay the Open Access publication charges for this article was provided by NIH Grant U10AA008401. Funding Information: This national collaborative study is supported by the NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). Genotyping was carried out using the facilities of the Center for Medical Genomics at Indiana University School of Medicine, which is supported in part by the Indiana Genomics Initiative of Indiana University (INGENw); INGEN is supported in part by The Lilly Endowment, Inc.",
year = "2008",
month = jun,
day = "15",
doi = "10.1093/hmg/ddn068",
language = "English",
volume = "17",
pages = "1783--1789",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "12",
}