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Independent associations of TOMM40 and APOE variants with body mass index.

Publication ,  Journal Article
Kulminski, AM; Loika, Y; Culminskaya, I; Huang, J; Arbeev, KG; Bagley, O; Feitosa, MF; Zmuda, JM; Christensen, K; Yashin, AI ...
Published in: Aging cell
February 2019

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 variants in Alzheimer's disease was suggested, comparative contribution of the TOMM40-APOE variants in the regulation of body weight remains elusive. We examined additive effects of rs2075650 and rs157580 TOMM40 variants and rs429358 and rs7412 APOE 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 ; and β = 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 and β = -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 older individuals, β = 0.58, 95% confidence interval (CI) = -1.18, 2.35, p = 5.18 × 10-1 for 3,068 individuals aged ≤30 years and β = -4.28, CI = -5.65, -2.92, p = 7.71 × 10-10 for 6,052 individuals aged >80 years. TOMM40 and APOE variants are independently and additively associated with BMI. The APOE ε4-coding rs429358 polymorphism is associated with BMI in older individuals but not in younger individuals.

Duke Scholars

Published In

Aging cell

DOI

EISSN

1474-9726

ISSN

1474-9718

Publication Date

February 2019

Volume

18

Issue

1

Start / End Page

e12869

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Multivariate Analysis
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Middle Aged
  • Membrane Transport Proteins
  • Linkage Disequilibrium
  • Humans
  • Genotype
  • Genetic Association Studies
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kulminski, A. M., Loika, Y., Culminskaya, I., Huang, J., Arbeev, K. G., Bagley, O., … Long Life Family Study Research Group, . (2019). Independent associations of TOMM40 and APOE variants with body mass index. Aging Cell, 18(1), e12869. https://doi.org/10.1111/acel.12869
Kulminski, Alexander M., Yury Loika, Irina Culminskaya, Jian Huang, Konstantin G. Arbeev, Olivia Bagley, Mary F. Feitosa, et al. “Independent associations of TOMM40 and APOE variants with body mass index.Aging Cell 18, no. 1 (February 2019): e12869. https://doi.org/10.1111/acel.12869.
Kulminski AM, Loika Y, Culminskaya I, Huang J, Arbeev KG, Bagley O, et al. Independent associations of TOMM40 and APOE variants with body mass index. Aging cell. 2019 Feb;18(1):e12869.
Kulminski, Alexander M., et al. “Independent associations of TOMM40 and APOE variants with body mass index.Aging Cell, vol. 18, no. 1, Feb. 2019, p. e12869. Epmc, doi:10.1111/acel.12869.
Kulminski AM, Loika Y, Culminskaya I, Huang J, Arbeev KG, Bagley O, Feitosa MF, Zmuda JM, Christensen K, Yashin AI, Long Life Family Study Research Group. Independent associations of TOMM40 and APOE variants with body mass index. Aging cell. 2019 Feb;18(1):e12869.
Journal cover image

Published In

Aging cell

DOI

EISSN

1474-9726

ISSN

1474-9718

Publication Date

February 2019

Volume

18

Issue

1

Start / End Page

e12869

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Multivariate Analysis
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Middle Aged
  • Membrane Transport Proteins
  • Linkage Disequilibrium
  • Humans
  • Genotype
  • Genetic Association Studies
  • Developmental Biology