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Linkage scan of nicotine dependence in the University of California, San Francisco (UCSF) Family Alcoholism Study

Published online by Cambridge University Press:  01 July 2010

I. R. Gizer*
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA
C. L. Ehlers
Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, CA, USA
C. Vieten
California Pacific Medical Center, San Francisco, CA, USA
K. L. Seaton-Smith
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
H. S. Feiler
Department of Laboratory Medicine, University of California, San Francisco, CA, USA
J. V. Lee
School of Molecular and Cell Biology, University of Illinois, Urbana–Champaign, IL, USA
S. K. Segall
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
D. A. Gilder
Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, CA, USA
K. C. Wilhelmsen
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA Department of Neurology, Carolina Genome Center, University of North Carolina, Chapel Hill, NC, USA
*Address for correspondence: I. R. Gizer, Ph.D., University of North Carolina at Chapel Hill, 120 Mason Farm Road, Room 5015 Genetic Medicine Building CB 7264, Chapel Hill, NC27599-7264, USA. (Email:



Nicotine dependence has been shown to represent a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder though only a limited number of the findings have been replicated.


In the present study, a genome-wide linkage scan for nicotine dependence was conducted in a community sample of 950 probands and 1204 relatives recruited through the University of California, San Francisco (UCSF) Family Alcoholism Study. A modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) with additional questions that probe nicotine use was used to derive DSM-IV nicotine dependence diagnoses.


A locus on chromosome 2q31.1 at 184 centiMorgans nearest to marker D2S2188 yielded a logarithm (base 10) of odds (LOD) score of 3.54 (point-wise empirical p=0.000012). Additional peaks of interest were identified on chromosomes 2q13, 4p15.33-31, 11q25 and 12p11.23-21. Follow-up analyses were conducted examining the contributions of individual nicotine dependence symptoms to the chromosome 2q31.1 linkage peak as well as examining the relationship of this chromosomal region to alcohol dependence.


The present report suggests that chromosome 2q31.1 confers risk to the development of nicotine dependence and that this region influences a broad range of nicotine dependence symptoms rather than a specific facet of the disorder. Further, the results show that this region is not linked to alcohol dependence in this population, and thus may influence nicotine dependence specifically.

Original Articles
Copyright © Cambridge University Press 2010

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