Genome-wide search for genes affecting the risk for alcohol dependence

Reich, Theodore; Edenberg, Howard J.; Goate, Alison; Williams, Jeff T.; Rice, John P.; Eerdewegh, Paul Van; Foroud, Tatiana; Hesselbrock, Victor; Schuckit, Marc A.; Bucholz, Kathleen K.; Porjesz, Bernice; Li, Ting Kai; Conneally, P. Michael; Nürnberger, John I.; Tischfield, Jay A.; Crowe, Raymond R.; Cloninger, C. Robert; Wu, William; Shears, Shantia; Carr, Kristie; Crose, Candice; Willig, Chris; Begleiter, Henri

doi:10.1002/(sici)1096-8628(19980508)81:3<207::aid-ajmg1>3.0.co;2-t

Cited by 679 publications

(459 citation statements)

References 28 publications

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“…Genotyping was carried out in laboratories at Indiana University and Washington University in St. Louis using radioactive and fluorescence-based detection systems, as described previously (Reich et al, 1998). The current analyses are based on a map of 315 autosomal microsatellite markers with an average intermarker distance of 11.5 cM.…”

Section: Genotyping and Analysismentioning

confidence: 99%

Linkage Analyses of IQ in the Collaborative Study on the Genetics of Alcoholism (COGA) Sample

et al. 2005

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Intelligence, as measured by standardized psychological tests, has been shown to be highly heritable, though identifying specific genes influencing general intelligence has proven difficult. We conducted genome-wide linkage analyses to identify chromosomal regions containing genes influencing intelligence, as measured by WAIS full-scale IQ (FSIQ), performance IQ (PIQ) and verbal IQ (VIQ). Non-parametric multipoint linkage analyses were conducted with Merlin-regress software, using a sample of 1,111 genotyped and phenotyped individuals from 201 families, ascertained as part of the Collaborative Study on the Genetics of Alcoholism (COGA). The strongest evidence of linkage was obtained for FSIQ on chromosome 6 (LOD=3.28, 12 cM) near the marker D6S1006. This region was also implicated with suggestive linkage in a recently published genome screen of IQ in Australian and Dutch twin pairs, and it has been implicated in linkage studies of developmental dyslexia. Our findings provide further support that chromosome 6p contains gene(s) affecting intelligence.

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Section: Genotyping and Analysismentioning

confidence: 99%

Linkage Analyses of IQ in the Collaborative Study on the Genetics of Alcoholism (COGA) Sample

et al. 2005

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“…Probands were recruited through treatment units. A description of the COGA ascertainment procedure can be found in Reich et al (1998) and Bierut et al (2004). Not all pedigrees included members who participated in the neuropsychiatric battery; those that did not were dropped from this study.…”

Section: Subjects and Samplesmentioning

confidence: 99%

“…Allele frequencies were estimated by COGA using maximum likelihood in Mendel, while marker order and distances were determined using CRIMAP. Full details can be found in Reich et al (1998). We used Merlin's error checking algorithm, based on detecting double recombinants, to classify 1907 of a total of 839,069 individual genotypes as unlikely and marked those genotypes as missing.…”

Section: Genotypingmentioning

confidence: 99%

“…For testing linkage of alcohol dependence along chromosomes 11 and 14 we used Genehunter 2 with non-parametric linkage (Kruglyak et al, 1996;Kruglyak and Lander, 1998). We followed the COGA definition of alcohol dependence, namely DSM-III-R and Feighner criteria positive (Reich et al, 1998), yielding three groups: ''pure unaffected,'' ''unaffected with some symptoms,'' and ''pure affected.'' MEGA2 (Mukhopadhyay et al, 1999) was used for data reformatting.…”

Section: Statistical Genetic Analysismentioning

confidence: 99%

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Cognitive Traits Link to Human Chromosomal Regions

et al. 2005

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: Human cognition in normal and disease states is both environmentally and genetically mediated. Except for measures of language-specific abilities, however, few cognitive measures have been associated with specific genes or chromosomal regions. We performed genome-wide linkage analysis of five neuropsychological tests in the Collaborative Study on Genetics of Alcoholism sample. The sample included 1579 individuals (53% female, 76% White Non-Hispanic) in 217 families. There were 390 markers with mean inter-marker distance of 9.6 cM. Performance on the Digit Symbol Substitution Test, a component of the Wechsler Adult Intelligence Scale-R, showed significant linkage to 14q11.2 and suggestive linkage to 14q 24.2. This test of sustained visual attention also involves visual-motor coordination and executive functions. Performance on the WAIS-R Digit Span Test of immediate memory and mental flexibility showed suggestive linkage to 11q 25. Although the validity of these results beyond populations with a susceptibility for alcohol dependence is unclear, these results are among the first linkage results for non-language components of cognition.

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“…Independent genome-wide linkage studies have been conducted in samples composed predominantly of Euro-Americans (Reich et al 1998;Saccone et al 2000) and the American Indian population analyzed in this study ). Both studies provided modest evidence for a locus contributing to alcohol dependence in the region of the ADH gene cluster on chromosome 4q, despite the fact that neither population possesses ADH1B*47His and ALDH2-2.…”

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confidence: 99%

Allelic variation at alcohol metabolism genes ( ADH1B , ADH1C , ALDH2 ) and alcohol dependence in an American Indian population

et al. 2003

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Enzymes encoded by two gene families, alcohol dehydrogenase ( ADH) and aldehyde dehydrogenase ( ALDH), mediate alcohol metabolism in humans. Allelic variants have been identified that alter metabolic rates and influence risk for alcoholism. Specifically, ADH1B*47His (previously ADH2-2) and ALDH2-2 have been shown to confer protection against alcoholism, presumably through accumulation of acetaldehyde in the blood and a resultant 'flushing response' to alcohol consumption. In the current study, variants at ADH1B (previously ADH2), ADH1C (previously ADH3), and ALDH2 were assayed in DNA extracts from participants belonging to a Southwest American Indian tribe ( n=490) with a high prevalence of alcoholism. Each subject underwent a clinical interview for diagnosis of alcohol dependence, as well as evaluation of intermediate phenotypes such as binge drinking and flushing response to alcohol consumption. Detailed haplotypes were constructed and tested against alcohol dependence and related intermediate phenotypes using both association and linkage analysis. ADH and ALDH variants were also assayed in three Asian and one African population (no clinical data) in order to provide an evolutionary context for the haplotype data. Both linkage and association analysis identified several ADH1C alleles and a neighboring microsatellite marker that affected risk of alcohol dependence and were also related to binge drinking. These data strengthen the support for ADH as a candidate locus for alcohol dependence and suggest further productive study.

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Genome-wide search for genes affecting the risk for alcohol dependence

Cited by 679 publications

References 28 publications

Linkage Analyses of IQ in the Collaborative Study on the Genetics of Alcoholism (COGA) Sample

Linkage Analyses of IQ in the Collaborative Study on the Genetics of Alcoholism (COGA) Sample

Cognitive Traits Link to Human Chromosomal Regions

Allelic variation at alcohol metabolism genes ( ADH1B , ADH1C , ALDH2 ) and alcohol dependence in an American Indian population

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