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Chunk #7 — Human studies

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The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks.
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has been associated with susceptibility to alcohol dependence [35]. Two SNPs in the 3' flanking region of the gene encoding peroxisomal trans-2-enoyl-CoA reductase, which is a key enzyme for the peroxisomal fatty acid chain elongation pathway, achieved genome-wide significance for alcohol dependence in a study of German males [31]. A GWAS on pooled DNA samples from individuals with a lifetime history of alcohol dependence, nicotine dependence and co-morbid alcohol/nicotine dependence in an Australian population [28] identified three SNPs that reached genome-wide significance for co-morbid alcohol/nicotine dependence. The implicated genes were: (1) the gene encoding MAP/microtubule affinity-regulating kinase 1 (MARK1), which is a kinase involved in the phosphorylation of microtubule-associated proteins; (2) the gene encoding DEAD box polypeptide 6 (DDX6), which is a putative RNA helicase; and (3) KIAA1409, which encodes a component of the NALCN Na+ channel complex. A family-based association analysis for alcohol dependence that utilized both COGA and the Australian twin-family samples implicated the genes encoding endothelin receptor type B (EDNRB), Usher syndrome 2A (USH2A), TCDD-inducible poly(ADP-ribose) polymerase (TIPARP), monoamine oxidase A, Na+/K+ transporting ATPase interacting 2 (NKAIN2), and Down syndrome cell adhesion molecule like 1 (DSCAML1) [32], with four SNPs in DSCAML1 reaching genome-wide significance. A GWAS