Suggestive linkages between markers on human 1p32-p22 and body fat and insulin levels in the Quebec Family Studies

A single-gene rodent mutation (diabetes) and a quantitative trait locus (dietary obese 1) mapped to the mid portion of mouse chromosome 4 have been related to obesity and/or insulin levels. Synteny relationships place their putative human homologs on 1p31 and 1p35-p31, respectively. In 137 sibships of adult brothers and sisters from the Quebec Family Study, genetic linkages between seven microsatellite markers from 1p32-p22 and various obesity- and diabetes-related quantitative phenotypes were examined using single locus sibpair linkage analysis. Suggestive linkages were observed between markers D1S476 and body mass index (p=0.05), fat mass (p=0.02), the sum of six skinfolds (p=0.02), the insulin area after an oral glucose tolerance test (p=0.02), and between the neighboring marker D1S200 and body mass index (p=0.03), and fat mass (p=0.009). Suggestive linkages were also observed between the more telomeric markers D1S193 and body mass index (p=0.03), and between the neighboring marker D1S197 and fasting insulin level (p=0.05). No linkage was observed with the trunk to extremity skinfolds ratio. These linkages suggest that human homologs of the mouse diabetes or dietary obese 1 and/or other genes in this interval on chromosome 1 play a role in the regulation of body mass, body composition, and insulin levels, but not of subcutaneous fat distribution.