Genome-wide linkage analysis for smoking-related regions, with replication in two ethnically diverse populations.

As part of the Genetic Epidemiology Network of Arteriopathy, hypertensive sibships were collected and smoking behavior recorded. Using an affected sibpair design and genome-wide microsatellite data markers ( approximately 10 cM coverage), we identified 214 non-Hispanic White sibships (502 sibpairs) from Rochester, Minnesota (M (age) [SD] = 55.68 years [10.56]) and 206 Black sibships (376 sibpairs) from Jackson, Mississippi (M (age) = 57.97 [8.94]), who had smoked for at least 3 years, and performed nonparametric linkage analysis using GENEHUNTER. We found evidence of linkage on chromosome 3 in both Whites (LOD = 1.76@109 cM) and Blacks (LOD = 2.03@122 cM). Each of these peaks had a secondary smaller peak at 140-147 cM that was statistically suggestive only in the Black sample (LOD = 1.4). The peak for the combined samples was suggestive of strong linkage (LOD = 3.24@124 cM). Additional suggestive peaks (LOD>1.3) were found in the White (chromosomes 8 [26 cM] and 19 [36 cM]) and Black sibships (chromosome 10 [153 cM]) but did not overlap with corresponding regions in the other ethnic group. This is the first study to identify a chromosomal region that has replicate evidence of linkage to smoking in two independent samples of similar size differing both geographically and ethnically. The gene for serotonin receptor 1F (HTR1F) is located in the region of the chromosome 3 linkage signal, representing at least one potential candidate gene. Fine mapping may well provide useful new information about genetic factors underlying nicotine dependence.