Lachman et al18 studied a mixed US sample of 305 OD-affected sibling pairs, and identified selleck chemical Sorafenib evidence for linkage on a region of chromosome 14 overlying the neurexin 3 gene (NRXN3). They also identified a male-specific
linkage peak on chromosome 10q. Finally, Glatt et al19 studied a sample of nearly 400 independent affected sibling pairs ascertained in China near the Golden Triangle, one of Asia’s largest illicit opium-producing areas, but did not identify any strongly -supported Inhibitors,research,lifescience,medical linkage signals, despite the presumed genetic homogeneity of the sample. The strongest signal they observed was on chromosome 4q. There have been numerous genome -wide linkage scans for smoking and related phenotypes, reviewed in ref 20. Hanet al21 completed genome scan meta-analysis (GSMA) of genome -wide linkage scans for nicotine dependence (ND) and
related traits, pooling all available independent Inhibitors,research,lifescience,medical genome scan results on smoking behavior. To minimize locus heterogeneity, subgroup analyses of the smoking behavior Inhibitors,research,lifescience,medical assessed by the Fagerstrom Test for Nicotine dependence (FTND) and maximum number of cigarettes smoked in a 24-hour period (MaxCigs24) were also carried out. Fifteen genome scan results were available for analysis, including 10 253 subjects in 3 404 families. The primary GSMA across all smoking behavior identified a genome -wide “suggestive” linkage in chromosome 17q24.3-q25.3. But the strongest result derived from
the subgroup analysis of MaxCigs24 (including 966 families with 3 273 subjects), which identified a genome-wide Inhibitors,research,lifescience,medical significant linkage in 20q13.12-q13.32. CHRNA4, a strongly supported ND candidate gene, is located in this interval; Li et al22 previously reported on association of CHRNA4 variants to ND. A high level of statistical support Inhibitors,research,lifescience,medical for a genetic linkage is very valuable, but the ultimate proof that a disease-influencing locus underlies a statistical linkage peak is the identification of a risk gene in the peak that accounts for the linkage signal. The next step is typically genetic association analysis, ie, evaluation of a set of markers that map under the linkage peak for association with the trait. Genetic association provides another degree of statistical evidence, but eventually, proof of a disease-gene Carfilzomib relationship must rely on demonstration of a functional effect of a variant or variants at the risk locus. ND is the furthest of all drug-dependence (DD) traits along this pathway, with numerous loci supported on the basis of statistical genetic association evidence, and some of these loci have received the higher level of support of functional data. Association selleck studies Strategy for single-nucleotide polymorphism (SNP) selection plays a key role in association study outcome.