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; M 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-Vidal; A Wong; K Meidtner; R P Middelberg; R J Strawbridge; L Christiansen; 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; Thorkild Sorensen; FTO-Mortality Collaborating Group

doi: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

E Zimmermann, L H Ängquist, S S Mirza, J H Zhao, D I Chasman, K Fischer, Q Qi, A V Smith, M 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, 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, Thorkild Sorensen, FTO-Mortality Collaborating Group

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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; 0.32 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 language	English
Pages (from-to)	327-40
Number of pages	14
Journal	Obesity Reviews
Volume	16
Issue number	4
DOIs	https://doi.org/10.1111/obr.12263
Publication status	Published - Apr 2015

Keywords

Adiposity
Body Mass Index
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Humans
Obesity
Observational Studies as Topic
Polymorphism, Single Nucleotide
Proteins
Waist Circumference
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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10.1111/obr.12263

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1 Finished

MRC UoB UNITE Unit - Programme 1
Davey Smith, G.
1/06/13 → 31/03/18
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Professor Yoav Ben-Shlomo
- Y.Ben-Shlomobristol.acuk
- Bristol Medical School (PHS) - Professor of Clinical Epidemiology
- Bristol Poverty Institute
- Bristol Population Health Science Institute
- Cancer
- Bristol Neuroscience
- Centre for Academic Primary Care
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Professor George Davey Smith
- KZ.Davey-Smithbristol.acuk
- MRC Integrative Epidemiology Unit
- Bristol Medical School (PHS) - Professor of Clinical Epidemiology
Person: Academic , Member, Group lead
Professor Nicholas John Timpson
- N.J.Timpsonbristol.acuk
- Bristol Medical School (PHS) - Professor of Genetic Epidemiology
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
- Cancer
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Cite this

Zimmermann, E., Ängquist, L. H., Mirza, S. S., Zhao, J. H., Chasman, D. I., Fischer, K., Qi, Q., Smith, A. V., Thinggaard, M., 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., ... FTO-Mortality Collaborating Group (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, 16(4), 327-40. https://doi.org/10.1111/obr.12263

@article{4530a32b08d84ce8a0e96d7244ed9e4d,

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 = "Adiposity, Body Mass Index, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Obesity, Observational Studies as Topic, Polymorphism, Single Nucleotide, Proteins, Waist Circumference, Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",

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 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 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 Thorkild Sorensen and {FTO-Mortality Collaborating Group}",

note = "{\textcopyright} 2015 World Obesity.",

year = "2015",

month = apr,

doi = "10.1111/obr.12263",

language = "English",

volume = "16",

pages = "327--40",

journal = "Obesity Reviews",

issn = "1467-7881",

publisher = "Wiley",

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, 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, Sorensen, T & FTO-Mortality Collaborating Group 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, vol. 16, no. 4, pp. 327-40. https://doi.org/10.1111/obr.12263

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, 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 - Sorensen, Thorkild

AU - FTO-Mortality Collaborating Group

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 - Adiposity

KW - Body Mass Index

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Humans

KW - Obesity

KW - Observational Studies as Topic

KW - Polymorphism, Single Nucleotide

KW - Proteins

KW - Waist Circumference

KW - Journal Article

KW - Meta-Analysis

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/obr.12263

DO - 10.1111/obr.12263

M3 - Article (Academic Journal)

C2 - 25752329

VL - 16

SP - 327

EP - 340

JO - Obesity Reviews

JF - Obesity Reviews

SN - 1467-7881

IS - 4

ER -

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

Keywords

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MRC UoB UNITE Unit - Programme 1

Profiles

Professor Yoav Ben-Shlomo

Professor George Davey Smith

Professor Nicholas John Timpson

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