TY - JOUR T1 - Progressive influence of body mass index-associated genetic markers in rural Gambians JF - Journal of Medical Genetics JO - J Med Genet SP - 375 LP - 380 DO - 10.1136/jmedgenet-2014-102784 VL - 52 IS - 6 AU - Anthony J Fulford AU - Ken K Ong AU - Cathy E Elks AU - Andrew M Prentice AU - Branwen J Hennig Y1 - 2015/06/01 UR - http://jmg.bmj.com/content/52/6/375.abstract N2 - Background In populations of European ancestry, the genetic contribution to body mass index (BMI) increases with age during childhood but then declines during adulthood, possibly due to the cumulative effects of environmental factors. How the effects of genetic factors on BMI change with age in other populations is unknown. Subjects and methods In a rural Gambian population (N=2535), we used a combined allele risk score, comprising genotypes at 28 ‘Caucasian adult BMI-associated’ single nucleotide polymorphisms (SNPs), as a marker of the genetic influence on body composition, and related this to internally-standardised z-scores for birthweight (zBW), weight-for-height (zWT-HT), weight-for-age (zWT), height-for-age (zHT), and zBMI cross-sectionally and longitudinally. Results Cross-sectionally, the genetic score was positively associated with adult zWT (0.018±0.009 per allele, p=0.034, N=1426) and zWT-HT (0.025±0.009, p=0.006), but not with size at birth or childhood zWT-HT (0.008±0.005, p=0.11, N=2211). The effect of the genetic score on zWT-HT strengthened linearly with age from birth through to late adulthood (age interaction term: 0.0083 z-scores/allele/year; 95% CI 0.0048 to 0.0118, p=0.0000032). Conclusions Genetic variants for obesity in populations of European ancestry have direct relevance to bodyweight in nutritionally deprived African settings. In such settings, genetic obesity susceptibility appears to regulate change in weight status throughout the life course, which provides insight into its potential physiological role. ER -