GENOMEWIDE SEARCH FOR GENES INFLUENCING PERCENT BODY-FAT IN PIMA-INDIANS - SUGGESTIVE LINKAGE AT CHROMOSOME 11Q21-Q22

On the basis of accumulating evidence that obesity has a substantial g enetic component, a genomewide search fur linkages of DNA markers to p ercent body fat is ongoing in Pima Indians, a population with a very h igh prevalence of obesity, An initial screen oi: the genome (>600 mark ers in 874 individuals) has been completed using highly polymorphic ma rkers (mean heterozygosity = .67), Reported here are the sib-pair link age results for percent body fat (277 siblings), the best available in dicator of overall obesity, Single-marker linkages to percent body fat were evaluated by sib-pair analysis for quantitative traits, From the se analyses, the best evidence of genes influencing body fat came from markers at chromosome 11q21-q22 and 3p24.2-p22 (P = .001; LOD = 2.0), Regions flanking these markers were further investigated by multipoin t linkage. The evidence for linkage at 11q21-q22 increased to P = .000 2 (LOD = 2.8), peaking between markers D11S2000 and D11S2366, Evidence for linkage at 3p24.2-p22 did nor change, No association was detected for any marker in the region, Although several genes are known in the 11q21-q22 region, none have been implicated as candidate genes for ob esity.