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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

Zimmermann, E.; Angquist, L. H.; Mirza, S. S.; Zhao, J. H.; Chasman, D. I.; Fischer, K.; Qi, Q.; Smith, A. V.; Thinggaard, M. and Jarczok, M. N., et al. (2015) In Obesity Reviews 16(4). p.327-340
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,... (More)
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<1x10(-32)), WC (n=152,631; 0.76cm; 0.68-0.84, P<1x10(-32)) and FMI (n=48,192; 0.17kgm(-2); 0.13-0.22, P=1.0x10(-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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
keywords
FTO, meta-analysis, mortality, obesity
in
Obesity Reviews
volume
16
issue
4
pages
327 - 340
publisher
Wiley-Blackwell
external identifiers
  • wos:000351612400006
  • scopus:84925584409
ISSN
1467-7881
DOI
10.1111/obr.12263
language
English
LU publication?
yes
id
a569f7c8-8280-46b6-9a87-42fcad8b1728 (old id 5402973)
date added to LUP
2015-06-01 09:22:14
date last changed
2017-08-13 03:04:46
@article{a569f7c8-8280-46b6-9a87-42fcad8b1728,
  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&lt;1x10(-32)), WC (n=152,631; 0.76cm; 0.68-0.84, P&lt;1x10(-32)) and FMI (n=48,192; 0.17kgm(-2); 0.13-0.22, P=1.0x10(-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.},
  author       = {Zimmermann, E. and Angquist, L. H. and Mirza, S. S. and Zhao, J. H. and Chasman, D. I. and Fischer, K. and Qi, Q. and Smith, A. V. and Thinggaard, M. and Jarczok, M. N. and Nalls, M. A. and Trompet, S. and Timpson, N. J. and Schmidt, B. and Jackson, A. U. and Lyytikainen, L. P. and Verweij, N. and Mueller-Nurasyid, M. and Vikstrom, M. and Marques-Vidal, P. and Wong, A. and Meidtner, K. and Middelberg, R. P. and Strawbridge, R. J. and Christiansen, L. and Kyvik, K. O. and Hamsten, A. and Jaaskelainen, T. and Tjonneland, A. and Eriksson, J. G. and Whitfield, J. B. and Boeing, H. and Hardy, R. and Vollenweider, P. and Leander, K. and Peters, A. and van der Harst, P. and Kumari, M. and Lehtimaki, T. and Meirhaeghe, A. and Tuomilehto, J. and Joeckel, K. -H. and Ben-Shlomo, Y. and Sattar, N. and Baumeister, S. E. and Smith, G. Davey and Casas, J. P. and Houston, D. K. and Maerz, W. and Christensen, K. and Gudnason, V. and Hu, F. B. and Metspalu, A. and Ridker, P. M. and Wareham, N. J. and Loos, R. J. F. and Tiemeier, H. and Sonestedt, Emily and Sorensen, T. I. A.},
  issn         = {1467-7881},
  keyword      = {FTO,meta-analysis,mortality,obesity},
  language     = {eng},
  number       = {4},
  pages        = {327--340},
  publisher    = {Wiley-Blackwell},
  series       = {Obesity Reviews},
  title        = {Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults},
  url          = {http://dx.doi.org/10.1111/obr.12263},
  volume       = {16},
  year         = {2015},
}