Search

Background: 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., Method: 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., Results: 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., Conclusions: 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.

Ample data suggest that alcohol dependence represents a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder. In the present study, a genome-wide linkage scan for alcohol dependence was conducted in a community sample of 565 probands and 1080 first-degree relatives recruited through the UCSF Family Alcoholism Study. The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was used to derive DSM-IV alcohol dependence diagnoses. Although no loci achieved genome-wide significance (i.e., LOD score > 3.0), several linkage peaks of interest (i.e., LOD score > 1.0) were identified. When the strict DSM-IV alcohol dependence diagnosis requiring the temporal clustering of symptoms served as the phenotype, linkage peaks were identified on chromosomes 1p36.31-p36.22, 2q37.3, 8q24.3, and 18p11.21-p11.2. When the temporal clustering of symptoms was not required, linkage peaks were again identified on chromosomes 1p36.31-p36.22 and 8q24.3 as well as novel loci on chromosomes 1p22.3, 2p24.3-p24.1, 9p24.1-p23, and 22q12.3-q13.1. Follow-up analyses were conducted by performing linkage analysis for the 12 alcohol dependence symptoms assessed by the SSAGA across the support intervals for the observed linkage peaks. These analyses demonstrated that different collections of symptoms often assessing distinct aspects of alcohol dependence (e.g., uncontrollable drinking and withdrawal vs. tolerance and drinking despite health problems) contributed to each linkage peak and often yielded LOD scores exceeding that reported for the alcohol dependence diagnosis. Such findings provide insight into how specific genomic regions may influence distinct aspects of alcohol dependence., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The current study evaluated the heritability of personality traits and psychopathology symptoms assessed by the Minnesota Multiphasic Personality Inventory 2nd Edition (MMPI-2) in a family-based sample selected for alcohol dependence. Participants included 950 probands and 1,204 first-degree relatives recruited for the University of California at San Francisco (UCSF) Family Alcoholism Study. Heritability estimates for MMPI-2 scales ranged from .25 to .49. When alcohol dependence was used as a covariate, heritability estimates remained significant but generally declined. However, when the MMPI-2 scales were used as covariates to estimate the heritability of alcohol dependence, the scales measuring antisocial behavior, depressive symptoms, and addictive behavior led to moderate increases in the heritability of alcohol dependence. This suggests that the scales may explain some of the non-genetic variance in the alcohol dependence diagnosis in this population when used as covariates, and thus may serve to produce a more homogeneous and heritable alcohol-dependence phenotype.