Genomic regions linked to alcohol consumption in the Framingham Heart Study

Bergen, Andrew W.; Yang, Xiaohong R.; Bai, Yan; Beerman, Michael; Goldstein, Alisa M.; Goldin, Lynn R.

doi:10.1186/1471-2156-4-s1-s101

Cited by 52 publications

(68 citation statements)

References 23 publications

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“…Of these 10 significant or highly significant linkages for smoking quantity, eight of them located on chromosomes 1, 4, 7, 8, 11, 16, 17, and 20 were also reported by one or more research groups [22][23][24][25] previously with the FHS smoking data at a nominal significance level, with a P-value of around 0.05 or LOD score between 1.0 and 2.0, except for the results reported by our group 25 in which we found significant evidence for linkage on chromosome 11 (pointwise Pvalue ¼ 10 À6 ) and suggestive evidence on chromosomes 4, 7, and 17 with a pointwise P-value of less than 0.0017. Nevertheless, our study does not represent a simple replication of those early works.…”

Section: Discussionmentioning

confidence: 93%

“…3 Recently, several research groups have performed linkage analyses with the smoking data of the FHS that were made available through the Genetic Analysis Workshop (GAW) 13. [22][23][24][25] In aggregate, these studies reported approximately 29 potential linkage regions for the smoking behavior. These potential linkage regions were located on most of the 22 autosomal chromosomes except chromosomes 3, 10, 18, and 19 (no genotypic data were available on the sex chromosomes).…”

Section: Introductionmentioning

confidence: 99%

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Mapping and verification of susceptibility loci for smoking quantity using permutation linkage analysis

Wang

2005

Pharmacogenomics J

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Nicotine dependence is the most prevalent form of drug addiction in the US and throughout the world. Epidemiological studies demonstrate that genetics accounts for at least 50% of the liability to nicotine dependence. However, there have been very limited linkage studies providing convincing evidence of susceptibility genomic loci for this disorder. In this study, we conducted genome-wide permutation linkage analyses on the smoking data collected between 1970 and 1972 of the Framingham Heart Study (FHS) to account for the abnormality associated with the smoking quantity (defined as the number of cigarettes smoked per day). We used empirical thresholds obtained from permutation tests to determine the significance of each genomic region. The variance component method implemented in SOLAR was used for the analysis. Under the empirical genome-wide thresholds determined specifically for the FHS smoking data, we found two highly or near-highly significant linkages of nicotine dependence on chromosomes 1 and 4 (P ¼ 0.001) and eight significant linkages on chromosomes 3,7,8,9,11,16,17, and 20 (Po0.05). These findings strongly indicate that some of these regions may harbor susceptibility loci for nicotine dependence. Further analysis of these positive regions by fine mapping and/or association analysis is warranted. To our knowledge, this study presents the most convincing linkage evidence for nicotine dependence in the field.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Mapping and verification of susceptibility loci for smoking quantity using permutation linkage analysis

Wang

2005

Pharmacogenomics J

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“…Although the prevalence of smoking has decreased significantly in many countries, particularly among men, the number of highly dependent smokers has not declined correspondingly. 28 In previous linkage analyses, smoking behavior as a phenotype has been defined in several different ways: average 7,15 or maximum 29,30 number of cigarettes smoked per day, ever smoking, 31 habitual smoking 17,18 and total number of cigarette packs per day for 1 year. 14 Similarly, ND can be defined in various ways, the most commonly used definitions being based on the DSM-IV 32 and the FTND.…”

Section: Discussionmentioning

confidence: 99%

Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background

et al. 2007

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The significant worldwide health burden introduced by tobacco smoking highlights the importance of studying the genetic determinants of smoking behavior and the key factor sustaining compulsive smoking, that is, nicotine dependence (ND). We have here addressed the genetic background of smoking in a special study sample of twins, harmonized for early life events and specifically ascertained for smoking from the nationwide twin cohort of the genetically unique population of Finland. The twins and their families were carefully examined for extensive phenotype profiles and a genomewide scan was performed to identify loci behind the smoking status, ND and the comorbid phenotype of ND and alcohol use in 505 individuals from 153 families. We replicated previous linkage findings on 10q (max logarithm of the odds (LOD) 3.12) for a smoker phenotype, and on 7q and 11p (max LOD 2.50, and 2.25, respectively) for the ND phenotype. The loci linked for ND also showed evidence for linkage for the comorbid phenotype. Our study provides confirmatory evidence for the involvement of these genome regions in the genetic etiology of smoking behavior and ND and for the first time associates drinking and smoking to a shared locus on 10q.

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“…[22][23][24][25][26][27][28][29][30][31][32][33][34] Only a few of the results of these studies have converged convincingly, with the major linkage peak produced by a number of studies being poorly, if at all, supported by subsequent data (e.g., see [22][23][24][25][26] ). Indeed, assemblies of current results from at least some linkage-based genomes can produce results that cover the majority of the genome with data that derive from at least some reported linkage peak in at least one study (C Johnson, GR Uhl, unpublished observations, 2005).…”

Section: The Scope Of Current Molecular Genetic Data For Addictionsmentioning

confidence: 99%

Molecular genetics of addiction vulnerability

Uhl

2006

NeuroRX

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Summary:Classical genetic studies document strong complex genetic contributions to abuse of multiple addictive substances, to mnemonic processes that are likely to include those involved in substance dependence, and to the volumes of brain gray matter in regions that are likely to contribute to mnemonic/ cognitive and to addictive processes. The working idea that these three heritable phenotypes are likely to share some of the same complex genetic underpinnings is presented. This review contains association-based molecular genetic studies of addiction that largely derive from my laboratory and their fit with linkage data from other laboratories. These combined results now identify many of the loci and genes that contain allelic variants that are likely to provide the heritable components of human addiction vulnerability. These data are also likely to have broad implications for neurotherapeutics. Drugs with potential abuse liabilities are widely used for indications that include pain, anxiety, sleep, seizure, and attentional disorders. There is increasing nonmedical use of these prescribed substances. Increasing information about addiction vulnerability gene variants should help to improve management of risks of dependence in individuals who receive such therapeutics. In addition, since mnemonic components that correlate well with individual differences in brain regional volumes are likely to play major roles in addiction processes, many addiction vulnerability genes are also good candidates to contribute to individual differences in mnemonic processes. Recently elucidation of addiction-associated haplotypes for the "cell adhesion" Nr-CAM gene illustrate several of these points.

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Genomic regions linked to alcohol consumption in the Framingham Heart Study

Cited by 52 publications

References 23 publications

Mapping and verification of susceptibility loci for smoking quantity using permutation linkage analysis

Mapping and verification of susceptibility loci for smoking quantity using permutation linkage analysis

Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background

Molecular genetics of addiction vulnerability

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