FTO influences on longitudinal BMI over childhood and adulthood and modulation on relationship between birth weight and longitudinal BMI

Abstract

SNP rs9939609 within the fat mass and obesity associated gene (FTO) is strongly associated with adult body mass index (BMI). However, influences of FTO on longitudinal BMI change from childhood to adulthood have not been examined. Knowledge is limited on FTO, modulating the association between birth weight and longitudinal change of BMI. This longitudinal study examined SNPs of FTO in 658 white subjects from childhood (3-17 years) to adulthood (18-45 years). No significant associations of FTO SNPs with either birth weight or longitudinal BMI over childhood were noted after multiple-test adjustment. However, three SNPs (rs9939609, rs17820875 and rs860713) with different inheritance patterns were identified to be associated with longitudinal BMI over adulthood after Bonferroni adjustment (P = 5.3 × 10(-5), 2.0 × 10(-4) and 0.001). In addition, interactions were discovered between birth weight and SNPs of rs17820875 (P = 0.001) and rs860713 (0.002). A negative association between birth weight and adult BMI were found in risk genotype AG of rs17820875 and GG of rs860713 in contrast to positive associations in other genotypes. These findings led to the conclusion that lower birth weight predisposes to higher adult BMI depending on FTO risk genotypes. Our studies underscore the importance of FTO influences on obesity and provide insights into the evolution of the long-term burden of obesity.

Effects of a High-Protein/Low-Carbohydrate Diet versus a Standard Hypocaloric Diet on Weight and Cardiovascular Risk Factors: Role of a Genetic Variation in the rs9939609 <b><i>FTO</i></b> Gene Variant

“…This single-nucleotide polymorphism is located in the first intron of the FTO gene at a position of 52.38 Mbp, where sequence is strongly conserved across species [19]. Several studies demonstrated that A allele carriers of rs9939609 have a higher body weight than carriers homozygous for the wild-type T allele [20,21], as indicated by our results.…”

Longitudinal Replication Studies of GWAS Risk SNPs Influencing Body Mass Index over the Course of Childhood and Adulthood

“…We previously confirmed that FTO tag SNPs, including rs9939609, were associated with longitudinal adulthood BMI [12]. In this study, we extended the test to 23 additional GWAS-significant SNPs that were genotyped in the Bogalusa Heart Study cohort.…”

“…However, no previous study provided the kind of direct evidence for an association between FTO and birth weight that was observed in this study. The FTO candidate SNPs (rs6499640, rs1121980, and rs8050136) were located at the 5′ end, upstream of the tag SNPs (rs9939609, rs17820875, and rs860713) that were explored previously [12] (Figure 2). These findings indicate that different regions of FTO are involved in childhood and adulthood obesity development; the upstream variant (rs6499640) was found to influence childhood BMI, and the downstream variants (rs1121980, rs8050136, rs9939609 [12], rs17820875 [12], and rs860713 [12]) were found to influence adulthood BMI.…”

“…The FTO candidate SNPs (rs6499640, rs1121980, and rs8050136) were located at the 5′ end, upstream of the tag SNPs (rs9939609, rs17820875, and rs860713) that were explored previously [12] (Figure 2). These findings indicate that different regions of FTO are involved in childhood and adulthood obesity development; the upstream variant (rs6499640) was found to influence childhood BMI, and the downstream variants (rs1121980, rs8050136, rs9939609 [12], rs17820875 [12], and rs860713 [12]) were found to influence adulthood BMI. The risk variants for adulthood BMI, rs1121980, rs8050136, and rs9939609 [12], located between the first two exons of FTO, had strong pairwise LD (r 2 ≥0.85 ).…”

“…To address these questions, we conducted a longitudinal replication study in the Bogalusa Heart Study cohort, using BMI data collected from 1973 to the present. We previously identified the longitudinal effects of FTO tag variants associated with birth weight [12]. In this follow-up study, we will examine 23 additional GWAS-significant SNPs and explore their joint effects using a heuristic forward searching strategy.…”