Linkage of body mass index to chromosome 20 in Utah pedigrees

Several linkage studies have hinted at the existence of an obesity predispo sition locus on chromosome 20, but none of these studies has produced concl usive results. Therefore, we analyzed 48 genetic markers on chromosome 20 f or linkage to severe obesity (BMI greater than or equal to 35) in 103 exten ded Utah pedigrees (1,711 individuals), all of which had strong aggregation of severe obesity. A simple dominant model produced a maximum multipoint h eterogeneity LOD score of 3.5 at D20S438 (55.1 cM). Two additional analyses were per-formed. First, a one-gene, two-mutation model (with one dominant mutation and one recessive mutation) increased the LOD score to 4.2. Second , a two-locus model (with one locus dominant and one recessive) generated a multipoint LOD score of 4.9. We conclude that one or more severe obesity p redisposing genes lie within an interval of approx. 10 cM on chromosome 20. This study generated significant LOD scores which confirm suggestive linka ge reports from previous studies. In addition, our analyses suggest that th e predisposing gene(s) is localized very near the chromosome 20 centromere.