Independent associations of TOMM40 and APOE variants with body mass index

• DOI: 10.1111/acel.12869
• Publication Date: 2018-11-21T15:31:56Z
• Authors: Alexander M. Kulm...; Yury Loika; Irina Culminskaya; Jian Huang; Konstantin G. Arbeev; Olivia Bagley; Mary F. Feitosa; Joseph M. Zmuda; Kaare Christensen; Anatoliy I. Yashin
• Keywords: Apolipoprotein E; Minor allele frequency

Abstract The TOMM40‐APOE variants are known for their strong, antagonistic associations with Alzheimer's disease and body weight. While a stronger role of the APOE than TOMM40 in was suggested, comparative contribution regulation weight remains elusive. We examined additive effects rs2075650 rs157580 rs429358 rs7412 coding ε2/ε3/ε4 polymorphism on mass index (BMI) age‐aggregated age‐stratified cohort‐specific cohort‐pooled analysis 27,863 Caucasians aged 20–100 years from seven longitudinal studies. Minor alleles rs2075650, rs429358, were individually associated BMI ( β = −1.29, p 3.97 × 10 −9 ; −1.38, 2.78 −10 0.58, 3.04 −2 , respectively). Conditional identified independent BMI‐lowering minor −0.63, 3.99 −0.94, 2.17 −3 Polygenic mega‐analysis heterozygotes −1.68, 3.00 ), strongest association heterozygous allele homozygous carriers −4.11, ). four polymorphisms (rs2075650, rs157580, rs429358) BMI‐increasing (rs7412) genotypes BMI. Age‐stratified conditional revealed well‐powered support differential heterozygote younger older individuals, 95% confidence interval (CI) −1.18, 2.35, 5.18 −1 3,068 individuals ≤30 −4.28, CI −5.65, −2.92, 7.71 6,052 >80 years. independently additively ε4‐coding is but not individuals.