Zimmermann, E and Ängquist, LH and Mirza, SS and Zhao, JH and Chasman, DI and Fischer, K and Qi, Q and Smith, AV and Thinggaard, M and Jarczok, MN and Nalls, MA and Trompet, S and Timpson, NJ and Schmidt, B and Jackson, AU and Lyytikäinen, LP and Verweij, N and Mueller‐Nurasyid, M and Vikström, M and Marques‐Vidal, P and Wong, A and Meidtner, K and Middelberg, RP and Strawbridge, RJ and Christiansen, L and Kyvik, KO and Hamsten, A and Jääskeläinen, T and Tjønneland, A and Eriksson, JG and Whitfield, JB and Boeing, H and Hardy, R and Vollenweider, P and Leander, K and Peters, A and van der Harst, P and Kumari, M and Lehtimäki, T and Meirhaeghe, A and Tuomilehto, J and Jöckel, K‐H and Ben‐Shlomo, Y and Sattar, N and Baumeister, SE and Davey Smith, G and Casas, JP and Houston, DK and März, W and Christensen, K and Gudnason, V and Hu, FB and Metspalu, A and Ridker, PM and Wareham, NJ and Loos, RJF and Tiemeier, H and Sonestedt, E and Sørensen, TIA (2015) Is the adiposity‐associated <scp><i>FTO</i></scp> gene variant related to all‐cause mortality independent of adiposity? Meta‐analysis of data from 169,551 <scp>C</scp>aucasian adults. Obesity Reviews, 16 (4). pp. 327-340. DOI https://doi.org/10.1111/obr.12263
Zimmermann, E and Ängquist, LH and Mirza, SS and Zhao, JH and Chasman, DI and Fischer, K and Qi, Q and Smith, AV and Thinggaard, M and Jarczok, MN and Nalls, MA and Trompet, S and Timpson, NJ and Schmidt, B and Jackson, AU and Lyytikäinen, LP and Verweij, N and Mueller‐Nurasyid, M and Vikström, M and Marques‐Vidal, P and Wong, A and Meidtner, K and Middelberg, RP and Strawbridge, RJ and Christiansen, L and Kyvik, KO and Hamsten, A and Jääskeläinen, T and Tjønneland, A and Eriksson, JG and Whitfield, JB and Boeing, H and Hardy, R and Vollenweider, P and Leander, K and Peters, A and van der Harst, P and Kumari, M and Lehtimäki, T and Meirhaeghe, A and Tuomilehto, J and Jöckel, K‐H and Ben‐Shlomo, Y and Sattar, N and Baumeister, SE and Davey Smith, G and Casas, JP and Houston, DK and März, W and Christensen, K and Gudnason, V and Hu, FB and Metspalu, A and Ridker, PM and Wareham, NJ and Loos, RJF and Tiemeier, H and Sonestedt, E and Sørensen, TIA (2015) Is the adiposity‐associated <scp><i>FTO</i></scp> gene variant related to all‐cause mortality independent of adiposity? Meta‐analysis of data from 169,551 <scp>C</scp>aucasian adults. Obesity Reviews, 16 (4). pp. 327-340. DOI https://doi.org/10.1111/obr.12263
Zimmermann, E and Ängquist, LH and Mirza, SS and Zhao, JH and Chasman, DI and Fischer, K and Qi, Q and Smith, AV and Thinggaard, M and Jarczok, MN and Nalls, MA and Trompet, S and Timpson, NJ and Schmidt, B and Jackson, AU and Lyytikäinen, LP and Verweij, N and Mueller‐Nurasyid, M and Vikström, M and Marques‐Vidal, P and Wong, A and Meidtner, K and Middelberg, RP and Strawbridge, RJ and Christiansen, L and Kyvik, KO and Hamsten, A and Jääskeläinen, T and Tjønneland, A and Eriksson, JG and Whitfield, JB and Boeing, H and Hardy, R and Vollenweider, P and Leander, K and Peters, A and van der Harst, P and Kumari, M and Lehtimäki, T and Meirhaeghe, A and Tuomilehto, J and Jöckel, K‐H and Ben‐Shlomo, Y and Sattar, N and Baumeister, SE and Davey Smith, G and Casas, JP and Houston, DK and März, W and Christensen, K and Gudnason, V and Hu, FB and Metspalu, A and Ridker, PM and Wareham, NJ and Loos, RJF and Tiemeier, H and Sonestedt, E and Sørensen, TIA (2015) Is the adiposity‐associated <scp><i>FTO</i></scp> gene variant related to all‐cause mortality independent of adiposity? Meta‐analysis of data from 169,551 <scp>C</scp>aucasian adults. Obesity Reviews, 16 (4). pp. 327-340. DOI https://doi.org/10.1111/obr.12263
Abstract
<jats:title>Summary</jats:title><jats:p>Previously, a single nucleotide polymorphism (<jats:styled-content style="fixed-case">SNP</jats:styled-content>), rs9939609, in the <jats:styled-content style="fixed-case"><jats:italic>FTO</jats:italic></jats:styled-content> gene showed a much stronger association with all‐cause mortality than expected from its association with body mass index (<jats:styled-content style="fixed-case">BMI</jats:styled-content>), body fat mass index (<jats:styled-content style="fixed-case">FMI</jats:styled-content>) and waist circumference (<jats:styled-content style="fixed-case">WC</jats:styled-content>). This finding implies that the <jats:styled-content style="fixed-case">SNP</jats:styled-content> 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 <jats:styled-content style="fixed-case">C</jats:styled-content>aucasians among whom 27,100 died during follow‐up. Linear regression showed that the minor allele of the <jats:styled-content style="fixed-case"><jats:italic>FTO</jats:italic> SNP</jats:styled-content> was associated with greater <jats:styled-content style="fixed-case">BMI</jats:styled-content> (<jats:italic>n</jats:italic> = 169,551; 0.32 kg m<jats:sup>−2</jats:sup>; 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 0.28–0.32, <jats:italic>P</jats:italic> < 1 × 10<jats:sup>−32</jats:sup>), <jats:styled-content style="fixed-case">WC</jats:styled-content> (<jats:italic>n</jats:italic> = 152,631; 0.76 cm; 0.68–0.84, <jats:italic>P</jats:italic> < 1 × 10<jats:sup>−32</jats:sup>) and <jats:styled-content style="fixed-case">FMI</jats:styled-content> (<jats:italic>n</jats:italic> = 48,192; 0.17 kg m<jats:sup>−2</jats:sup>; 0.13–0.22, <jats:italic>P</jats:italic> = 1.0 × 10<jats:sup>−13</jats:sup>). <jats:styled-content style="fixed-case">C</jats:styled-content>ox proportional hazard regression analyses for mortality showed that the hazards ratio (<jats:styled-content style="fixed-case">HR</jats:styled-content>) for the minor allele of the <jats:styled-content style="fixed-case"><jats:italic>FTO</jats:italic> SNPs</jats:styled-content> was 1.02 (1.00–1.04, <jats:italic>P</jats:italic> = 0.097), but the apparent excess risk was eliminated after adjustment for <jats:styled-content style="fixed-case">BMI</jats:styled-content> and <jats:styled-content style="fixed-case">WC</jats:styled-content> (<jats:styled-content style="fixed-case">HR</jats:styled-content>: 1.00; 0.98–1.03, <jats:italic>P</jats:italic> = 0.662) and for <jats:styled-content style="fixed-case">FMI</jats:styled-content> (<jats:styled-content style="fixed-case">HR</jats:styled-content>: 1.00; 0.96–1.04, <jats:italic>P</jats:italic> = 0.932). In conclusion, this study does not support that the <jats:styled-content style="fixed-case"><jats:italic>FTO</jats:italic> SNP</jats:styled-content> is associated with all‐cause mortality independently of the adiposity phenotypes.</jats:p>
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FTO; meta-analysis; mortality; obesity |
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Faculty of Social Sciences Faculty of Social Sciences > Institute for Social and Economic Research |
| SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
| Depositing User: | Unnamed user with email elements@essex.ac.uk |
| Date Deposited: | 15 May 2015 14:07 |
| Last Modified: | 30 Oct 2024 19:59 |
| URI: | http://repository.essex.ac.uk/id/eprint/13696 |