Independent associations of TOMM40 and APOE variants with body mass index

We examined additive effects of rs2075650 and rs157580TOMM40 variants and rs429358 and rs7412APOE variants coding the ε2/ε3/ε4 polymorphism on body mass index (BMI) in age‐aggregated and age‐stratified cohort‐specific and cohort‐pooled analysis of 27,863 Caucasians aged 20–100 years from seven longitudinal studies. Minor alleles of rs2075650, rs429358, and rs7412 were individually associated with BMI (β =  −1.29,p = 3.97 × 10−9;β =  −1.38,p = 2.78 × 10−10; andβ =  0.58,p = 3.04 × 10−2, respectively). Conditional analysis with rs2075650 and rs429358 identified independent BMI ‐lowering associations for minor alleles (β =  −0.63,p = 3.99 × 10−2 andβ =  −0.94,p = 2.17 × 10−3, respectively). Polygenic mega ‐analysis identified additive effects of the rs2075650 and rs429358 heterozygotes (β =  −1.68,p = 3.00 × 10−9), and the strongest BMI ‐lowering association for the rs2075650 heterozygous and rs429358 minor allele homozygous carriers (β =  −4.11,p = 2.78 × 10−3). Conditional analysis with four polymorphisms identified independent BMI ‐lowering (rs2075650, rs157580, and rs429358) and BMI‐increasing (rs7412) associations of heterozygous genotypes with BMI. Age‐stratified conditional analysis revealed well‐powered support for a differential and independent association of the rs429358 heterozygote with BMI in younger and old er individuals,β =  0.58, 95% confidence interv...

Source: Aging Cell - November 21, 2018 Category: Cytology Authors: Alexander M. Kulminski, Yury Loika, Irina Culminskaya, Jian Huang, Konstantin G. Arbeev, Olivia Bagley, Mary F. Feitosa, Joseph M. Zmuda, Kaare Christensen, Anatoliy I. Yashin, Long Life Family Study Research Group Tags: ORIGINAL PAPER Source Type: research