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; K. Christensen; V. Gudnason; F. B. Hu; A. Metspalu; P. M. Ridker; N. J. Wareham; R. J F Loos; H. Tiemeier; E. Sonestedt; T. I A Sørensen; M. Orho-Melander; C. Zillikens; Ikram A. Ikram; A. Hofman; J. Luan; K. T. Khaw; L. M. Rose; K. Läll; R. Mägi; L. Qi; Q. Sun; Harris T.B. Harris; L. J. Launer; G. Eiriksdottir; M. E. Kleber; G. Delgado; Y. Liu; M. Garcia; A. Teumer; H. Grabe; G. Homuth; Jukema J.W. Jukema; I. Ford; A. J. M. de Craen; J. Gallacher; J. Yarnell; A. A. Mahabadi; M. M. Nöthen; R. Erbel; H. M. Stringham; M. Boehnke; P. Amouyel; Ferrières J. Ferrières; D. Arveiler; Kähönen M. Kähönen; K. Nikus; Nieminen T. Nieminen; A. Sanchez; M. Kivimaki; van Vliet-Ostaptchouk J.V. van Vliet-Ostaptchouk; R. Hampel; B. Thorand; U. De Faire; Nyberg F. Nyberg; D. Kuh; N. G. Martin; G. W. Montgomery; A. C. Heath; P. A. F. Madden; C. Osmond; N. Pulizzi; N. Roswall; J. Halkjær; Overvad K. Overvad; Uusitupa M. Uusitupa; L. Kinnunen; J. Lindström; J. Saramies; S. Keinänen-Kiukaanniemi; H. Uusitalo; E. Hussi; Baldassarre D. Baldassarre; F. Veglia; S. Humphries; Tremoli E. Tremoli; B. Heitmann

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, K. Christensen, V. Gudnason, F. B. Hu, A. Metspalu, P. M. Ridker, N. J. Wareham, R. J F Loos, H. Tiemeier, E. Sonestedt, T. I A Sørensen, M. Orho-Melander, C. Zillikens, Ikram A. Ikram, A. Hofman, J. Luan, K. T. Khaw, L. M. Rose, K. Läll, R. Mägi, L. Qi, Q. Sun, Harris T.B. Harris, L. J. Launer, G. Eiriksdottir, M. E. Kleber, G. Delgado, Y. Liu, M. Garcia, A. Teumer, H. Grabe, G. Homuth, Jukema J.W. Jukema, I. Ford, A. J. M. de Craen, J. Gallacher, J. Yarnell, A. A. Mahabadi, M. M. Nöthen, R. Erbel, H. M. Stringham, M. Boehnke, P. Amouyel, Ferrières J. Ferrières, D. Arveiler, Kähönen M. Kähönen, K. Nikus, Nieminen T. Nieminen, A. Sanchez, M. Kivimaki, van Vliet-Ostaptchouk J.V. van Vliet-Ostaptchouk, R. Hampel, B. Thorand, U. De Faire, Nyberg F. Nyberg, D. Kuh, N. G. Martin, G. W. Montgomery, A. C. Heath, P. A. F. Madden, C. Osmond, N. Pulizzi, N. Roswall, J. Halkjær, Overvad K. Overvad, Uusitupa M. Uusitupa, L. Kinnunen, J. Lindström, J. Saramies, S. Keinänen-Kiukaanniemi, H. Uusitalo, E. Hussi, Baldassarre D. Baldassarre, F. Veglia, S. Humphries, Tremoli E. Tremoli, B. Heitmann

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

7 Citationer (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-32), WC (n=152,631; 0.76cm; 0.68-0.84, P-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.

Originalsprog	Engelsk
Tidsskrift	Obesity Reviews
Vol/bind	16
Udgave nummer	4
Sider (fra-til)	327-340
Antal sider	14
ISSN	1467-7881
DOI	https://doi.org/10.1111/obr.12263
Status	Udgivet - 1 apr. 2015
Udgivet eksternt	Ja

Adgang til dokumentet

10.1111/obr.12263

AUB Link

Søg efter materialet i Aalborg Universitetsbiblioteks søgemaskine

Andre filer og links

http://www.scopus.com/inward/record.url?scp=84925584409&partnerID=8YFLogxK

Citationsformater

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., ... Heitmann, B. (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), 327-340. https://doi.org/10.1111/obr.12263

@article{93c78df1e6b842b5903d60a9aef2e3b5,

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; 0.32kgm-2; 95% CI 0.28-0.32, P-32), WC (n=152,631; 0.76cm; 0.68-0.84, P-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.",

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 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 and V. Gudnason and Hu, {F. B.} and A. Metspalu and Ridker, {P. M.} and Wareham, {N. J.} and Loos, {R. J F} and H. Tiemeier and E. Sonestedt and S{\o}rensen, {T. I A} and M. Orho-Melander and C. Zillikens and {A. Ikram}, Ikram and A. Hofman and J. Luan and Khaw, {K. T.} and Rose, {L. M.} and K. L{\"a}ll and R. M{\"a}gi and L. Qi and Q. Sun and {T.B. Harris}, Harris and Launer, {L. J.} and G. Eiriksdottir and Kleber, {M. E.} and G. Delgado and Y. Liu and M. Garcia and A. Teumer and H. Grabe and G. Homuth and {J.W. Jukema}, Jukema and I. Ford and {M. de Craen}, {A. J.} and J. Gallacher and J. Yarnell and Mahabadi, {A. A.} and N{\"o}then, {M. M.} and R. Erbel and Stringham, {H. M.} and M. Boehnke and P. Amouyel and {J. Ferri{\`e}res}, Ferri{\`e}res and D. Arveiler and {M. K{\"a}h{\"o}nen}, K{\"a}h{\"o}nen and K. Nikus and {T. Nieminen}, Nieminen and A. Sanchez and M. Kivimaki and {J.V. van Vliet-Ostaptchouk}, {van Vliet-Ostaptchouk} and R. Hampel and B. Thorand and {De Faire}, U. and {F. Nyberg}, Nyberg and D. Kuh and Martin, {N. G.} and Montgomery, {G. W.} and Heath, {A. C.} and {F. Madden}, {P. A.} and C. Osmond and N. Pulizzi and N. Roswall and J. Halkj{\ae}r and {K. Overvad}, Overvad and {M. Uusitupa}, Uusitupa and L. Kinnunen and J. Lindstr{\"o}m and J. Saramies and S. Kein{\"a}nen-Kiukaanniemi and H. Uusitalo and E. Hussi and {D. Baldassarre}, Baldassarre and F. Veglia and S. Humphries and {E. Tremoli}, Tremoli and B. Heitmann",

year = "2015",

month = apr,

day = "1",

doi = "10.1111/obr.12263",

language = "English",

volume = "16",

pages = "327--340",

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, 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, KH, Ben-Shlomo, Y, Sattar, N, Baumeister, SE, Davey Smith, G, Casas, JP, Houston, DK, März, W, Christensen, K, Gudnason, V, Hu, FB, Metspalu, A, Ridker, PM, Wareham, NJ, Loos, RJF, Tiemeier, H, Sonestedt, E, Sørensen, TIA, Orho-Melander, M, Zillikens, C, A. Ikram, I, Hofman, A, Luan, J, Khaw, KT, Rose, LM, Läll, K, Mägi, R, Qi, L, Sun, Q, T.B. Harris, H, Launer, LJ, Eiriksdottir, G, Kleber, ME, Delgado, G, Liu, Y, Garcia, M, Teumer, A, Grabe, H, Homuth, G, J.W. Jukema, J, Ford, I, M. de Craen, AJ, Gallacher, J, Yarnell, J, Mahabadi, AA, Nöthen, MM, Erbel, R, Stringham, HM, Boehnke, M, Amouyel, P, J. Ferrières, F, Arveiler, D, M. Kähönen, K, Nikus, K, T. Nieminen, N, Sanchez, A, Kivimaki, M, J.V. van Vliet-Ostaptchouk, VV-O, Hampel, R, Thorand, B, De Faire, U, F. Nyberg, N, Kuh, D, Martin, NG, Montgomery, GW, Heath, AC, F. Madden, PA, Osmond, C, Pulizzi, N, Roswall, N, Halkjær, J, K. Overvad, O, M. Uusitupa, U, Kinnunen, L, Lindström, J, Saramies, J, Keinänen-Kiukaanniemi, S, Uusitalo, H, Hussi, E, D. Baldassarre, B, Veglia, F, Humphries, S, E. Tremoli, T & Heitmann, B 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, bind 16, nr. 4, s. 327-340. 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? 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 - Christensen, K.

AU - Gudnason, V.

AU - Hu, F. B.

AU - Metspalu, A.

AU - Ridker, P. M.

AU - Wareham, N. J.

AU - Loos, R. J F

AU - Tiemeier, H.

AU - Sonestedt, E.

AU - Sørensen, T. I A

AU - Orho-Melander, M.

AU - Zillikens, C.

AU - A. Ikram, Ikram

AU - Hofman, A.

AU - Luan, J.

AU - Khaw, K. T.

AU - Rose, L. M.

AU - Läll, K.

AU - Mägi, R.

AU - Qi, L.

AU - Sun, Q.

AU - T.B. Harris, Harris

AU - Launer, L. J.

AU - Eiriksdottir, G.

AU - Kleber, M. E.

AU - Delgado, G.

AU - Liu, Y.

AU - Garcia, M.

AU - Teumer, A.

AU - Grabe, H.

AU - Homuth, G.

AU - J.W. Jukema, Jukema

AU - Ford, I.

AU - M. de Craen, A. J.

AU - Gallacher, J.

AU - Yarnell, J.

AU - Mahabadi, A. A.

AU - Nöthen, M. M.

AU - Erbel, R.

AU - Stringham, H. M.

AU - Boehnke, M.

AU - Amouyel, P.

AU - J. Ferrières, Ferrières

AU - Arveiler, D.

AU - M. Kähönen, Kähönen

AU - Nikus, K.

AU - T. Nieminen, Nieminen

AU - Sanchez, A.

AU - Kivimaki, M.

AU - J.V. van Vliet-Ostaptchouk, van Vliet-Ostaptchouk

AU - Hampel, R.

AU - Thorand, B.

AU - De Faire, U.

AU - F. Nyberg, Nyberg

AU - Kuh, D.

AU - Martin, N. G.

AU - Montgomery, G. W.

AU - Heath, A. C.

AU - F. Madden, P. A.

AU - Osmond, C.

AU - Pulizzi, N.

AU - Roswall, N.

AU - Halkjær, J.

AU - K. Overvad, Overvad

AU - M. Uusitupa, Uusitupa

AU - Kinnunen, L.

AU - Lindström, J.

AU - Saramies, J.

AU - Keinänen-Kiukaanniemi, S.

AU - Uusitalo, H.

AU - Hussi, E.

AU - D. Baldassarre, Baldassarre

AU - Veglia, F.

AU - Humphries, S.

AU - E. Tremoli, Tremoli

AU - Heitmann, B.

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-32), WC (n=152,631; 0.76cm; 0.68-0.84, P-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-32), WC (n=152,631; 0.76cm; 0.68-0.84, P-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

UR - http://www.scopus.com/inward/record.url?scp=84925584409&partnerID=8YFLogxK

U2 - 10.1111/obr.12263

DO - 10.1111/obr.12263

M3 - Journal article

AN - SCOPUS:84925584409

SN - 1467-7881

VL - 16

SP - 327

EP - 340

JO - Obesity Reviews

JF - Obesity Reviews

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

Adgang til dokumentet

AUB Link

Andre filer og links

Fingeraftryk

Citationsformater