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Genome-Wide Scan of Obesity in Finnish Sibpairs Reveals Linkage to Chromosome Xq24¹

Department of Human Molecular Genetics, National Public Health Institute (M.Ö., L.P.), FIN-00300 Helsinki; Departments of Medicine (L.O., K.K.), Medical Genetics (L.P.), and Public Health (J.K.), University of Helsinki, FIN-00290 Helsinki; Department of Public Health and General Practice, University of Oulu (J.K.), FIN-90014 Oulu; Department of Public Health, University of Turku (M.K.), FIN-20520 Turku; Peijas Hospital (P.M.), FIN-01400 Vantaa; The Obesity Research Center, Helsinki University Central Hospital (A.R.), FIN-00290 Helsinki; and Department of Internal Medicine, University Hospital of Tampere (J.S.), FIN-33520 Tampere, Finland

Address all correspondence and requests for reprints to: Leena Peltonen, M.D., Ph.D., Department of Human Genetics, Gonda Neuroscience and Genetics Research Center, University of California, Room 6506, 695 Charles E. Young Drive South, Box 708822, Los Angeles, California 90095-7088. E-mail: lpeltonen{at}mednet.ucla.edu

Obesity is a multifactorial trait with evidence of a genetic component. Obesity is very common in all westernized countries, including Finland, where 10% of the adult population has a body mass index of 32 kg/m² or more. Here we report results from a three-stage genome-wide scan of obesity in 188 affected subjects (body mass index, 32 kg/m²) from 87 Finnish families. Initially, 374 markers with an average density of 10 centimorgans were genotyped. The strongest evidence for linkage to obesity was detected on chromosome Xq24, with the marker DXS6804 providing a maximum likelihood score (MLS) 3.14 in a model-free 2-point sibpair analysis. Fine-mapping in an extended sample set of 367 affected subjects from 166 families yielded a multipoint MLS of 3.48 over this X-chromosomal region. The Xq24 region contains a plausible candidate gene, serotonin 2C receptor, variants of which have been shown to predispose to obesity and type II diabetes in mice. Another chromosomal region also provided suggestive evidence of linkage, an area on 18q21, flanking the melanocortin-4 receptor, where a 2-point MLS of 2.42 with marker D18S1155 was obtained with a set of 367 affected subjects. In conclusion, our results in this Finnish study sample suggest that a locus on chromosome Xq24 influences the risk of obesity.

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