A QTL for genotype by sex interaction for anthropometric measurements in Alaskan Eskimos (GOCADAN study) on chromosome 19q12-13

Variation in anthropometric measurements due to sexual dimorphism can be the result of genotype by sex interactions (G×S). The purpose of this study was to examine the sex-specific genetic architecture in anthropometric measurements in Alaskan Eskimos from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Maximum likelihood-based variance components decomposition methods, implemented in SOLAR, were used for G×S analyses. Anthropometric measurements included BMI, waist circumference (WC), waist/height ratio, percent body fat (%BF), and subscapular and triceps skinfolds. Except for WC, mean values of all phenotypes were significantly different in men and women (P<0.05). All anthropometric measures were significantly heritable (P<0.001). In a preliminary analysis not allowing for G×S interaction, evidence of linkage was detected between markers D19S414 and D19S220 on chromosome 19 for WC (logarithm of odds (lod) = 3.5), %BF (lod = 1.7), BMI (lod = 2.4), waist/height ratio (lod = 2.5), subscapular (lod = 2.1), and triceps skinfolds (lod = 1.9). In subsequent analyses which allowed for G×S interaction, linkage was again found between these traits and the same two markers on chromosome 19 with significantly improved lod scores for: WC (lod = 4.5), %BF (lod = 3.8), BMI (lod = 3.5), waist/height ratio (lod = 3.2), subscapular (lod = 3.0), and triceps skinfolds (lod = 2.9). These results support the evidence of a G×S interaction in the expression of genetic effects resulting in sexual dimorphism in anthropometric phenotypes and identify the chromosome 19q12-13 region as important for adiposity-related traits in Alaskan Eskimos.