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Dopa decarboxylase is an enzyme of major importance for dopamine synthesis; it also plays a role in serotonin biosynthesis. Ma et al. (2005) studied DDC, the gene encoding this protein, in ND, based both on its physiology and its map location in an ND linkage peak they identified. They showed association between long-range DDC haplotypes and three correlated quantitative traits of smoking behavior using family-based association tests (FBATs) in families, each ascertained through an affected sibling pair for ND. Yu et al. (2006) replicated and extended these results, and reported an association of alleles and haplotypes at DDC with the DSM-IV diagnosis of ND or Fagerström Test for Nicotine Dependence score. They genotyped 18 SNPs spanning a region including DDC and the genes immediately flanking it, in the affected sibling pair sample recruited for opioid or cocaine dependence (i.e., the linkage sample described above). Evidence of association was observed with several SNPs for both traits. The most significant result was obtained for the relationship of Fagerström Test for Nicotine Dependence score to an SNP that maps to the same intron as an important DDC splice site. These findings were consistent with those of Ma et al. (2005), and served to localize the causative variants to the 3' end of the coding region.

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