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

E Zimmermann, L H Ängquist, S S Mirza, J H Zhao, D I Chasman, K Fischer, Q Qi, A V Smith, Mikael Thinggaard, M N Jarczok, M A Nalls, S Trompet, N J Timpson, B Schmidt, A U Jackson, L P Lyytikäinen, N Verweij, M Mueller-Nurasyid, M Vikström, P Marques-VidalA Wong, K Meidtner, R P Middelberg, R J Strawbridge, L Christiansen, FTO-Mortality Collaborating Group, K O Kyvik, A Hamsten, T Jääskeläinen, A Tjønneland, J G Eriksson, J B Whitfield, H Boeing, R Hardy, P Vollenweider, K Leander, A Peters, P van der Harst, M Kumari, T Lehtimäki, A Meirhaeghe, J Tuomilehto, K-H Jöckel, Y Ben-Shlomo, N Sattar, S E Baumeister, G Davey Smith, J P Casas, D K Houston, W März, Kaare Christensen

Research output: Contribution to journalJournal articleResearchpeer-review

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; 0.32 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.

Original languageEnglish
JournalObesity reviews : an official journal of the International Association for the Study of Obesity
Volume16
Issue number4
Pages (from-to)327-40
ISSN1467-7881
DOIs
Publication statusPublished - Apr 2015

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Adiposity
Single Nucleotide Polymorphism
Meta-Analysis
Body Mass Index
Fats
Alleles
Longitudinal Studies
Adipose Tissue
Linear Models
Regression Analysis

Cite this

Zimmermann, E ; Ängquist, L H ; Mirza, S S ; Zhao, J H ; Chasman, D I ; Fischer, K ; Qi, Q ; Smith, A V ; Thinggaard, Mikael ; Jarczok, M N ; Nalls, M A ; Trompet, S ; Timpson, N J ; Schmidt, B ; Jackson, A U ; Lyytikäinen, L P ; Verweij, N ; Mueller-Nurasyid, M ; Vikström, M ; Marques-Vidal, P ; Wong, A ; Meidtner, K ; Middelberg, R P ; Strawbridge, R J ; Christiansen, L ; FTO-Mortality Collaborating Group ; Kyvik, K O ; Hamsten, A ; Jääskeläinen, T ; Tjønneland, A ; Eriksson, J G ; Whitfield, J B ; 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, S E ; Davey Smith, G ; Casas, J P ; Houston, D K ; März, W ; Christensen, Kaare. / Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults. In: Obesity reviews : an official journal of the International Association for the Study of Obesity. 2015 ; Vol. 16, No. 4. pp. 327-40.
@article{e3318e76da2d432e8b7e7f955a8d6a5b,
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",
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; 0.32 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.",
keywords = "FTO, meta-analysis, mortality, obesity",
author = "E Zimmermann and {\"A}ngquist, {L H} and Mirza, {S S} and Zhao, {J H} and Chasman, {D I} and K Fischer and Q Qi and Smith, {A V} and Mikael 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 {FTO-Mortality Collaborating Group} 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 K-H J{\"o}ckel 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 Kaare Christensen",
note = "{\circledC} 2015 World Obesity.",
year = "2015",
month = "4",
doi = "10.1111/obr.12263",
language = "English",
volume = "16",
pages = "327--40",
journal = "Obesity Reviews",
issn = "1467-7881",
publisher = "Wiley-Blackwell",
number = "4",

}

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, Davey Smith, G, Casas, JP, Houston, DK, März, W & Christensen, K 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', Obesity reviews : an official journal of the International Association for the Study of Obesity, vol. 16, no. 4, pp. 327-40. https://doi.org/10.1111/obr.12263

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; Ängquist, L H; Mirza, S S; Zhao, J H; Chasman, D I; Fischer, K; Qi, Q; Smith, A V; Thinggaard, Mikael; Jarczok, M N; Nalls, M A; Trompet, S; Timpson, N J; Schmidt, B; Jackson, A U; Lyytikäinen, L P; Verweij, N; Mueller-Nurasyid, M; Vikström, M; Marques-Vidal, P; Wong, A; Meidtner, K; Middelberg, R P; Strawbridge, R J; Christiansen, L; FTO-Mortality Collaborating Group ; Kyvik, K O; Hamsten, A; Jääskeläinen, T; Tjønneland, A; Eriksson, J G; Whitfield, J B; 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, S E; Davey Smith, G; Casas, J P; Houston, D K; März, W; Christensen, Kaare.

In: Obesity reviews : an official journal of the International Association for the Study of Obesity, Vol. 16, No. 4, 04.2015, p. 327-40.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity?

T2 - Meta-analysis of data from 169,551 Caucasian adults

AU - Zimmermann, E

AU - Ängquist, L H

AU - Mirza, S S

AU - Zhao, J H

AU - Chasman, D I

AU - Fischer, K

AU - Qi, Q

AU - Smith, A V

AU - Thinggaard, Mikael

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 - FTO-Mortality Collaborating Group

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, Kaare

N1 - © 2015 World Obesity.

PY - 2015/4

Y1 - 2015/4

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; 0.32 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.

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; 0.32 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.

KW - FTO

KW - meta-analysis

KW - mortality

KW - obesity

U2 - 10.1111/obr.12263

DO - 10.1111/obr.12263

M3 - Journal article

C2 - 25752329

VL - 16

SP - 327

EP - 340

JO - Obesity Reviews

JF - Obesity Reviews

SN - 1467-7881

IS - 4

ER -