A Genome-Wide Search for Genes That Relate to a Low Level of Response to Alcohol

Authors

  • M. A. Schuckit,

    Corresponding author
    1. Department of Psychiatry, University of California, San Diego (MAS, JK, TLS); Indiana University (HJE, LF, TF); Washington University, St. Louis, Missouri (TR, LB, AG).
      Reprint requests: Marc A. Schuckit, MD, Department of Psychiatry (116A), University of California, San Diego and the Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161-2002; Fax: 858-552-7424; E-mail: mschuckit@ucsd.edu
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  • H. J. Edenberg,

    1. Department of Psychiatry, University of California, San Diego (MAS, JK, TLS); Indiana University (HJE, LF, TF); Washington University, St. Louis, Missouri (TR, LB, AG).
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  • J. Kalmijn,

    1. Department of Psychiatry, University of California, San Diego (MAS, JK, TLS); Indiana University (HJE, LF, TF); Washington University, St. Louis, Missouri (TR, LB, AG).
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  • L. Flury,

    1. Department of Psychiatry, University of California, San Diego (MAS, JK, TLS); Indiana University (HJE, LF, TF); Washington University, St. Louis, Missouri (TR, LB, AG).
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  • T. L. Smith,

    1. Department of Psychiatry, University of California, San Diego (MAS, JK, TLS); Indiana University (HJE, LF, TF); Washington University, St. Louis, Missouri (TR, LB, AG).
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  • T. Reich,

    1. Department of Psychiatry, University of California, San Diego (MAS, JK, TLS); Indiana University (HJE, LF, TF); Washington University, St. Louis, Missouri (TR, LB, AG).
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  • L. Bierut,

    1. Department of Psychiatry, University of California, San Diego (MAS, JK, TLS); Indiana University (HJE, LF, TF); Washington University, St. Louis, Missouri (TR, LB, AG).
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  • A. Goate,

    1. Department of Psychiatry, University of California, San Diego (MAS, JK, TLS); Indiana University (HJE, LF, TF); Washington University, St. Louis, Missouri (TR, LB, AG).
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  • T. Foroud

    1. Department of Psychiatry, University of California, San Diego (MAS, JK, TLS); Indiana University (HJE, LF, TF); Washington University, St. Louis, Missouri (TR, LB, AG).
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  • This national collaborative study is supported by NIH Grant U10AA08403 from NIAAA. This research also was supported by Grant 05526 from NIAAA, by Grant 5T32 MH18399 from NIMH, and by the Veterans Affairs Research Service.

  • The Collaborative Study on the Genetics of Alcoholism (COGA) (H. Begleiter, SUNY HSCB Principal Investigator, T. Reich, Washington University, Co-Principal Investigator) includes nine different centers where data collection, analysis, and/or storage takes place. The nine sites and principal investigators and co-investigators are Indiana University (T.-K. Li, J. Nurnberger Jr., P.M. Conneally, H. Edenberg); University of Iowa (R. Crowe, S. Kuperman); University of California at San Diego (M. Schuckit); University of Connecticut (V. Hesselbrock); State University of New York, Health Sciences Center at Brooklyn (B. Porjesz, H. Begleiter); Washington University in St. Louis (T. Reich, C.R. Cloninger, J. Rice, A. Goate); Howard University (R. Taylor); Rutgers University (J. Tischfield); and Southwest Foundation (L. Almasy).

Reprint requests: Marc A. Schuckit, MD, Department of Psychiatry (116A), University of California, San Diego and the Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161-2002; Fax: 858-552-7424; E-mail: mschuckit@ucsd.edu

Abstract

Background: The low level of response (LR) to alcohol is genetically influenced in both humans and animals, and a low LR is a characteristic of offspring of alcoholics that has been reported to predict alcoholism 10 and 15 years later. The genes that contribute to a low LR have not yet been identified.

Methods: A 12-item questionnaire that measures LR, the Self Rating of the Effects of Alcohol (SRE) instrument, was filled out by 745 individuals from the Collaborative Study on the Genetics of Alcoholism (COGA) for whom genetic material was available. These subjects were genotyped by using 336 markers with an average heterozygosity of 0.74 and an average intermarker distance of 10.5 cM. Both quantitative and qualitative nonparametric, sib-pair analyses were carried out for the SRE measure related to early drinking experiences.

Results: Correlations of SRE scores across related individuals were significant and between 0.16 and 0.22 for most values, compared with nonsignificant correlations of 0.03 or less among unrelated individuals. Linkage analyses performed by using the FIRST 5 variables (first five times alcohol is consumed) identified four chromosomal regions with lod scores ≥2.0 whose maximum was also near a marker. One of these chromosomal regions previously was linked to alcohol dependence in the COGA sample.

Conclusions: These data document the familial nature of a low LR to alcohol as measured by the SRE and suggest several chromosomal regions that might contribute to the phenomenon.

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