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

The FTO-Mortality Collaborating Group

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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; 0.32kgm-2; 95% CI 0.28-0.32, P<1×10-32), WC (n=152,631; 0.76cm; 0.68-0.84, P<1×10-32) and FMI (n=48,192; 0.17kgm-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.

Original languageEnglish (US)
Pages (from-to)327-340
Number of pages14
JournalObesity Reviews
Volume16
Issue number4
DOIs
StatePublished - Apr 1 2015

Fingerprint

Adiposity
Single Nucleotide Polymorphism
Meta-Analysis
Waist Circumference
Body Mass Index
Mortality
Genes
Fats
Alleles
Longitudinal Studies
Adipose Tissue
Linear Models
Regression Analysis
Phenotype

Keywords

  • FTO
  • Meta-analysis
  • Mortality
  • Obesity

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Endocrinology, Diabetes and Metabolism

Cite this

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

In: Obesity Reviews, Vol. 16, No. 4, 01.04.2015, p. 327-340.

Research output: Contribution to journalArticle

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abstract = "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; 0.32kgm-2; 95{\%} CI 0.28-0.32, P<1×10-32), WC (n=152,631; 0.76cm; 0.68-0.84, P<1×10-32) and FMI (n=48,192; 0.17kgm-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.",
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author = "{The FTO-Mortality Collaborating Group} and E. Zimmermann and {\"A}ngquist, {L. H.} and Mirza, {S. S.} and Zhao, {J. H.} and Chasman, {D. I.} and K. Fischer and Qibin Qi and Smith, {A. V.} and M. Thinggaard and Jarczok, {M. N.} and Nalls, {M. A.} and S. Trompet and Timpson, {N. J.} and B. Schmidt and Jackson, {A. U.} and Lyytik{\"a}inen, {L. P.} and N. Verweij and M. Mueller-Nurasyid and M. Vikstr{\"o}m and P. Marques-Vidal and A. Wong and K. Meidtner and Middelberg, {R. P.} and Strawbridge, {R. J.} and L. Christiansen and Kyvik, {K. O.} and A. Hamsten and T. J{\"a}{\"a}skel{\"a}inen and A. Tj{\o}nneland and Eriksson, {J. G.} and Whitfield, {J. B.} and H. Boeing and R. Hardy and P. Vollenweider and K. Leander and A. Peters and {van der Harst}, P. and M. Kumari and T. Lehtim{\"a}ki and A. Meirhaeghe and J. Tuomilehto and J{\"o}ckel, {K. H.} and Y. Ben-Shlomo and N. Sattar and Baumeister, {S. E.} and {Davey Smith}, G. and Casas, {J. P.} and Houston, {D. K.} and W. M{\"a}rz and K. Christensen",
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T1 - Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults

AU - The FTO-Mortality Collaborating Group

AU - Zimmermann, E.

AU - Ängquist, L. H.

AU - Mirza, S. S.

AU - Zhao, J. H.

AU - Chasman, D. I.

AU - Fischer, K.

AU - Qi, Qibin

AU - Smith, A. V.

AU - Thinggaard, M.

AU - Jarczok, M. N.

AU - Nalls, M. A.

AU - Trompet, S.

AU - Timpson, N. J.

AU - Schmidt, B.

AU - Jackson, A. U.

AU - Lyytikäinen, L. P.

AU - Verweij, N.

AU - Mueller-Nurasyid, M.

AU - Vikström, M.

AU - Marques-Vidal, P.

AU - Wong, A.

AU - Meidtner, K.

AU - Middelberg, R. P.

AU - Strawbridge, R. J.

AU - Christiansen, L.

AU - Kyvik, K. O.

AU - Hamsten, A.

AU - Jääskeläinen, T.

AU - Tjønneland, A.

AU - Eriksson, J. G.

AU - Whitfield, J. B.

AU - Boeing, H.

AU - Hardy, R.

AU - Vollenweider, P.

AU - Leander, K.

AU - Peters, A.

AU - van der Harst, P.

AU - Kumari, M.

AU - Lehtimäki, T.

AU - Meirhaeghe, A.

AU - Tuomilehto, J.

AU - Jöckel, K. H.

AU - Ben-Shlomo, Y.

AU - Sattar, N.

AU - Baumeister, S. E.

AU - Davey Smith, G.

AU - Casas, J. P.

AU - Houston, D. K.

AU - März, W.

AU - Christensen, K.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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; 0.32kgm-2; 95% CI 0.28-0.32, P<1×10-32), WC (n=152,631; 0.76cm; 0.68-0.84, P<1×10-32) and FMI (n=48,192; 0.17kgm-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.

AB - 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; 0.32kgm-2; 95% CI 0.28-0.32, P<1×10-32), WC (n=152,631; 0.76cm; 0.68-0.84, P<1×10-32) and FMI (n=48,192; 0.17kgm-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.

KW - FTO

KW - Meta-analysis

KW - Mortality

KW - Obesity

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