Segregation analysis of regional fat distribution in families from Andhra Pradesh, India.

Abstract

Segregation analysis was used to examine the major gene evidence for regional fat distribution and whether the effects of covariates such as energy variables (intake and expenditure) or total subcutaneous fat, impact on the major gene inference. The data consist of measurements made on 1691 individuals in 432 pedigrees residing in the Chittor district of Andhra Pradesh, India, during the period from January 1989 to February 1990. Fat distribution was computed as the ratio of trunk skinfold sum (subscapular + suprailiac + abdominal) to extremity skinfold sum (biceps + triceps + medial calf). The trunk/extremity skinfold ratio (TER) was also analyzed after adjusting for the amount of energy expended in various activities and energy intake (TER-E), as well as after adjusting for overall level of fatness as measured by the sum of six skinfolds (TER-SF6). Segregation analysis was applied using the unified model (POINTER). For the TER all of the conditions needed to satisfy a major gene hypothesis were met, and a putative recessive locus in the presence of a multifactorial component was inferred. Adjusting the TER for energy intake (EI) and energy expenditure (EE) did not change these results. However, adjusting for total subcutaneous fat did alter the results. Specifically, after removing the effects due to total fat, there was a major non-Mendelian effect (free tau s) with additional multifactorial influences, and with generation heterogeneity in both components. A putative major locus for fat distribution as indexed by the TER was found. However, further analyses suggested the hypothesis that this major gene may be primarily for total fat with secondary effects on fat distribution (that is, major gene pleiotropy). The possibility that there is a second locus that is modified by interactions with gender and age, and that impacts on the preferential accumulation of fat in the trunk vs extremity depots could be inferred.