AUTOSOMAL GENOMIC SCAN FOR LOCI LINKED TO OBESITY AND ENERGY-METABOLISM IN PIMA-INDIANS

An autosomal genomic scan to search for linkage to obesity and energy metabolism was completed in Pima Indians, a population prone to obesit y. Obesity was assessed by percent body fat (by hydrodensitometry) and fat distribution (the ratio of waist circumference to thigh circumfer ence). Energy metabolism was measured in;a respiratory chamber as 24-h metabolic rate, sleeping metabolic rate, and 24-h respiratory quotien t (24RQ), an indicator of the ratio of carbohydrate oxidation to fat o xidation. Five hundred sixteen microsatellite markers with a median sp acing of 6.4 cM were analyzed, in 362 siblings who had measurements of body composition and in 220 siblings who had measurements of energy m etabolism. These comprised 451 sib pairs in 127 nuclear families, for linkage analysis to obesity, and 236 sib pairs in 82 nuclear families, for linkage analysis to energy metabolism. Pointwise and multipoint m et:hods for regression of sib-pair differences in identity by descent, as well as a sibling-based variance-components method, were used to d etect linkage. LOD scores greater than or equal to 2 were found at 11q 21-q22, for percent body fat (LOD = 2.1; P = .001), at 11q23-q24, for 24-h energy expenditure (LOD = 2.0; P = .001), and at 1p31-p21 (LOD = 2.0) and 20q11.2 (LOD = 3.0; P = .0001), for 24RQ, by pointwise and mu ltipoint analysts. With the variance-components method, the highest LO D score (LOD = 2.3 P = .0006) was found at 18q21, for percent body fat , and at 1p31-p21 (LOD = 2.8; P = .0003), for 24RQ. Possible candidate genes include LEPR (leptin receptor), at 1p31, and ASIP (agouti-signa ling protein), at 20q11.2.