Laura J Bierut

..Alcoholism and substance dependence frequently co-occur. Accordingly, we evaluated the familial transmission of alcohol, marijuana, and cocaine dependence and habitual smoking in the Collaborative Study on the Genetics of Alcoholism...

..Sex differences in genetic effects were also studied...

..There also was no evidence for unequal transmission of DRD2 alleles for the phenotypes "ever smoker" or comorbid alcohol dependence and habitual smoking. This study does not support linkage of the DRD2 with smoking...

..The goal of this study was to examine the association of this variant with cocaine dependence...

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..We examined whether these genetic variants were associated with comorbid disorders and whether comorbid psychiatric disorders modified the genetic risk of nicotine dependence...

..Incorporation of logically chosen interaction parameters, such as AOS, into genetic models of substance use disorders may increase the degree of explained phenotypic variation and constitutes a promising avenue for gene discovery...

..In the present report, we extend the previous study by expanding our genotyping efforts significantly for these two genes...

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..Lastly, comprehensive genotyping and in vivo metabolism data are used to demonstrate that genome-wide significant associations between CPD and single nucleotide polymorphisms are the result of synthetic associations...

..The goal of this study was to identify predictors of problematic young adult alcohol use...

..The perceived bitterness of PROP has also been associated with oral sensation and drinking behaviors...

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..The aim of this study was to examine the abbreviated Desires for Alcohol Questionnaire (DAQ) with respect to component structure and concurrent validity...

..While replication is required, this study represents an important first step toward clarifying the biological underpinnings of cannabis dependence...

..05) and rs806380 (P = 0.009)]. Haplotype analyses revealed the association to be largely driven by the SNP rs806380. These results suggest a role for the cannabinoid receptor 1 gene in cannabis dependence...

..The nonsynonymous SNP rs16969968, a known risk variant in populations of European-descent, is also significantly associated with risk in African-Americans. Additional SNPs contribute to risk in distinct ways in these two populations...

..Many studies have found that earlier drinking initiation predicts higher risk of later alcohol and substance use problems, but the causal relationship between age of initiation and later risk of substance use disorder remains unknown...

..The prevalence of obesity has risen sharply in the United States in the past few decades. Etiologic links between obesity and substance use disorders have been hypothesized...

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..Some of this clustering may be due to the presence of a second segregating SNP that obliterates a XbaI site (the restriction enzyme used in the Affymetrix platform), resulting in a fragment too long (>1,000 bp) to be amplified...

..11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence...

..0 on chromosome 2 (3.2, 234 cM), 10 (2.4 and 2.6 at 60 cM and 116 cM) and 13 (2.1 at 64 cM). These regions may harbor genes that contribute to the biological basis of alcohol and drug dependence...

..Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968...

..Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments...

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..There was no association with other genes in the GABAA cluster on chromosome 4 with illicit drug dependence...

..However, increased information has a computational cost: SNP maps require 100 times as many iterations as microsatellites to produce stable estimates...

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..e., CPD versus Fagerström test for cigarette dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence...

..01, T91I P = 0.02, R37H P = 0.003), but the largest effect on in vitro receptor activity was seen in the presence of both CHRNB4 T91I and CHRNA3 R37H (P = 2 × 10(-6))...

..To extend the previously identified association between a single nucleotide polymorphism (SNP) in neuronal acetylcholine receptor subunit alpha-5 (CHRNA5) and nicotine dependence to current smoking and initial smoking-experience phenotypes...

..The present report sought to confirm the trends in AOD and to determine the extent to which they might account for secular trends in alcohol dependence...

..The results to date suggest that both common and drug-specific genetic influences play a role in the development of alcohol and nicotine dependence...

..A challenging problem after a genome-wide association study (GWAS) is to balance the statistical evidence of genotype-phenotype correlation with a priori evidence of biological relevance...

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..Methodologies that limit analyses of joint effects to variants that demonstrate association in single SNP analyses, or require a significant interaction term, will likely miss important joint effects...

..Furthermore, investigators should consider the specific disorder(s) being investigated and the ages of the children being studied when determining whether to include parent reports as part of study design...

..The relationship of nicotine dependence (ND) to smoking behavior and cessation has been well characterized. However, little is known about the association between smoking reduction (SR) and ND...

..We examined how these identified genetic variants relate to nicotine dependence defined by different categorical and dimensional measures...

..The objective of this study is to examine whether individuals who were legally permitted to drink prior to age 21 remained at elevated risk in adulthood...

..0001). The results of this study suggest that increasing the number of African Americans in genetic databases may be achieved by increasing efforts to locate and contact them...

..A better understanding of the etiology of nicotine addiction may help to increase the success rate of cessation and to decrease the massive morbidity and mortality associated with smoking...

..To study the association between cytochrome P450 2A6 (CYP2A6) genotype and metabolism of nicotine to cotinine, identify functional polymorphisms, and develop a predictive genetic model of nicotine metabolism...

..Traditional measures of imputation cannot effectively address these problems...

..We also considered the effect of high linkage disequilibrium (LD) in regions near the linkage peaks by analysing a "sparse" SNP map obtained by dropping some markers in high LD with other markers in those regions...

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..Data from genome-wide association studies and other microarrays may be used to identify CNVs by several different computer programs, but the reliability of the results has been questioned...

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..We examined this possibility by analyzing the association between NS and alcohol dependence in individuals at intermediate and high levels of familial risk for alcohol dependence...

..However, it remains unclear whether such patterns truly reflect secular trends or are confounded by age-dependent factors such as differential recall, differential mortality, and other effects...

..This combination of biological prioritization scores and LD tagging annotation will enable addiction researchers to supplement commercial SNP microarrays to ensure comprehensive coverage of biologically relevant regions...

..This study examined the associations between social, behavioral, and environmental factors and adolescent parenthood...

..These associations highlight the importance of understanding the genetics of substance dependence in the context of its multiple medical and psychiatric comorbidities...

..We sought to address this issue using data from a nationally representative U.S. sample of adolescents and young adults. Specifically, we analyzed the relationship between cigarette smoking, drinking, and AUDs...

..In this review, we discuss the challenges associated with harmonizing alcohol-consumption data from studies with widely different assessment instruments, with a particular focus on large-scale genetic studies...

..These associations highlight the importance of understanding the genetics of substance dependence in the context of its multiple medical and psychiatric comorbidities...

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..Describe differences in smoking behaviors associated with occupation, workplace rules against smoking, and workplace smoking cessation programs...

..Our results suggest that p34 may be a novel tumor suppressor gene involved in sporadic lung cancer but it seems not to be the candidate familial lung cancer susceptibility gene linked to chromosomal region 6q23-25...

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..6%), whereas 45% of African Americans carry the allele (MAF 26%), which makes it a much more significant risk factor in the African American population...

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..Combining the initial and replication samples further increased the evidence of linkage to this region, with a peak lod score of 2.8...

..These families were recruited as part of the Collaborative Study on the Genetics of Alcoholism (COGA)...

..These findings provide strong evidence that variants within or close to the CHRM2 locus influence risk for two common psychiatric disorders...

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..We also obtain evidence for epistatic interaction between a region on Chromosome 1 and one on Chromosome 15. Although alcoholism as a covariate does not have any effect on the linkage scan, it has an effect on the epistatic interaction...

..This article presents data regarding the familial nature of SRE-based scores among a sample of teenagers...

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..A Positron Emission Tomography (PET) study in high and low risk subjects will test GABAergic hypotheses of disinhibition in alcohol dependence. ..

..Data from this proposal will be become part of the NIDA Genetics Consortium to be made available to the scientific community. ..

..We hope to translate these basic biological and environmental studies into strategies to reduce the massive health burden of nicotine dependence. ..

..By comparing and contrasting findings in three datasets, a more thorough understanding of common and specific factors underlying human addiction will be developed. ..

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