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Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Publication ,  Journal Article
Zimmermann, E; Ängquist, LH; Mirza, SS; Zhao, JH; Chasman, DI; Fischer, K; Qi, Q; Smith, AV; Thinggaard, M; Jarczok, MN; Nalls, MA; Trompet, S ...
Published in: Obes Rev
April 2015

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

Duke Scholars

Published In

Obes Rev

DOI

EISSN

1467-789X

Publication Date

April 2015

Volume

16

Issue

4

Start / End Page

327 / 340

Location

England

Related Subject Headings

  • Waist Circumference
  • Proteins
  • Polymorphism, Single Nucleotide
  • Observational Studies as Topic
  • Obesity
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
  • Genetic Predisposition to Disease
  • Endocrinology & Metabolism
 

Citation

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Zimmermann, E., Ängquist, L. H., Mirza, S. S., Zhao, J. H., Chasman, D. I., Fischer, K., … Sørensen, T. I. A. (2015). Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults. Obes Rev, 16(4), 327–340. https://doi.org/10.1111/obr.12263
Zimmermann, E., L. H. Ängquist, S. S. Mirza, J. H. Zhao, D. I. Chasman, K. Fischer, Q. Qi, et al. “Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.Obes Rev 16, no. 4 (April 2015): 327–40. https://doi.org/10.1111/obr.12263.
Zimmermann E, Ängquist LH, Mirza SS, Zhao JH, Chasman DI, Fischer K, et al. Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults. Obes Rev. 2015 Apr;16(4):327–40.
Zimmermann, E., et al. “Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.Obes Rev, vol. 16, no. 4, Apr. 2015, pp. 327–40. Pubmed, doi:10.1111/obr.12263.
Zimmermann E, Ängquist LH, Mirza SS, Zhao JH, Chasman DI, Fischer K, Qi Q, Smith AV, Thinggaard M, Jarczok MN, Nalls MA, Trompet S, Timpson NJ, Schmidt B, Jackson AU, Lyytikäinen LP, Verweij N, Mueller-Nurasyid M, Vikström M, Marques-Vidal P, Wong A, Meidtner K, Middelberg RP, Strawbridge RJ, Christiansen L, FTO-Mortality Collaborating Group, Kyvik KO, Hamsten A, Jääskeläinen T, Tjønneland A, Eriksson JG, Whitfield JB, Boeing H, Hardy R, Vollenweider P, Leander K, Peters A, van der Harst P, Kumari M, Lehtimäki T, Meirhaeghe A, Tuomilehto J, Jöckel K-H, Ben-Shlomo Y, Sattar N, Baumeister SE, Smith GD, Casas JP, Houston DK, März W, Christensen K, Gudnason V, Hu FB, Metspalu A, Ridker PM, Wareham NJ, Loos RJF, Tiemeier H, Sonestedt E, Sørensen TIA. Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults. Obes Rev. 2015 Apr;16(4):327–340.
Journal cover image

Published In

Obes Rev

DOI

EISSN

1467-789X

Publication Date

April 2015

Volume

16

Issue

4

Start / End Page

327 / 340

Location

England

Related Subject Headings

  • Waist Circumference
  • Proteins
  • Polymorphism, Single Nucleotide
  • Observational Studies as Topic
  • Obesity
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
  • Genetic Predisposition to Disease
  • Endocrinology & Metabolism