Genome-wide scan of obesity in Finnish sibpairs reveals linkage to chromosome Xq24

Obesity is a multifactorial trait with evidence of a genetic component. Obe sity is very common in all westernized countries, including Finland, where 10% of the adult population has a body mass index of 32 kg/m(2) or more. He re we report results from a three-stage genome-wide scan of obesity in 188 affected subjects (body mass index, greater than or equal to 32 kg/m(2)) fr om 87 Finnish families. Initially, 374 markers with an average density of 1 0 centimorgans were genotyped. The strongest evidence for linkage to obesit y was detected on chromosome Xq24, with the marker DXS6804 providing a maxi mum likelihood score (MLS) 3.14 in a model-free a-point sibpair analysis. F ine-mapping in an extended sample set of 367 affected subjects from 166 fam ilies yielded a multipoint MLS of 3.48 over this X-chromosomal region. The Xq24 region contains a plausible candidate gene, seratonin 20 receptor, var iants of which have been shown to predispose to obesity and type II diabete s in mice. Another chromosomal region also provided suggestive evidence of linkage, an area on 18q21, flanking the melanocortin-4-receptor, where a X- point MLS of 2.42 with marker D18S1155 was obtained with a set of 367 affec ted subjects. In conclusion, our results in this Finnish study sample sugge st that a locus on chromosome Xq24 influences the risk of obesity.