Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
25752329
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.
© 2015 World Obesity.
DATE PUBLISHED
2015 Apr
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/12/03
accepted 2014/12/12
aheadofprint 2015/03/05
entrez 2015/03/11 06:00
pubmed 2015/03/11 06:00
medline 2015/12/29 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Zimmermann E Zimmermann E E Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, Denmark.
Ängquist LH Ängquist L H LH
Mirza SS Mirza S S SS
Zhao JH Zhao J H JH
Chasman DI Chasman D I DI
Fischer K Fischer K K
Qi Q Qi Q Q
Smith AV Smith A V AV
Thinggaard M Thinggaard M M
Jarczok MN Jarczok M N MN
Nalls MA Nalls M A MA
Trompet S Trompet S S
Timpson NJ Timpson N J NJ
Schmidt B Schmidt B B
Jackson AU Jackson A U AU
Lyytikäinen LP Lyytikäinen L P LP
Verweij N Verweij N N
Mueller-Nurasyid M Mueller-Nurasyid M M
Vikström M Vikström M M
Marques-Vidal P Marques-Vidal P P
Wong A Wong A A
Meidtner K Meidtner K K
Middelberg RP Middelberg R P RP
Strawbridge RJ Strawbridge R J RJ
Christiansen L Christiansen L L
FTO-Mortality Collaborating Group
Kyvik KO Kyvik K O KO
Hamsten A Hamsten A A
Jääskeläinen T Jääskeläinen T T
Tjønneland A Tjønneland A A
Eriksson JG Eriksson J G JG
Whitfield JB Whitfield J B JB
Boeing H Boeing H H
Hardy R Hardy R R
Vollenweider P Vollenweider P P
Leander K Leander K K
Peters A Peters A A
van der Harst P van der Harst P P
Kumari M Kumari M M
Lehtimäki T Lehtimäki T T
Meirhaeghe A Meirhaeghe A A
Tuomilehto J Tuomilehto J J
Jöckel KH Jöckel K-H KH
Ben-Shlomo Y Ben-Shlomo Y Y
Sattar N Sattar N N
Baumeister SE Baumeister S E SE
Davey Smith G Davey Smith G G
Casas JP Casas J P JP
Houston DK Houston D K DK
März W März W W
Christensen K Christensen K K
Gudnason V Gudnason V V
Hu FB Hu F B FB
Metspalu A Metspalu A A
Ridker PM Ridker P M PM
Wareham NJ Wareham N J NJ
Loos RJ Loos R J F RJ
Tiemeier H Tiemeier H H
Sonestedt E Sonestedt E E
Sørensen TI Sørensen T I A TI
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Orho-Melander M M
Zillikens C C
Ikram A A
Hofman A A
Luan J J
Khaw K T KT
Rose L M LM
Läll K K
Mägi R R
Qi L L
Sun Q Q
Harris T B TB
Launer L J LJ
Eiriksdottir G G
Kleber M E ME
Delgado G G
Liu Y Y
Garcia M M
Teumer A A
Grabe H H
Homuth G G
Jukema J W JW
Ford I I
de Craen A J M AJ
Gallacher J J
Yarnell J J
Mahabadi A A AA
Nöthen M M MM
Erbel R R
Stringham H M HM
Boehnke M M
Amouyel P P
Ferrières J J
Arveiler D D
Kähönen M M
Nikus K K
Nieminen T T
Sanchez A A
Kivimaki M M
van Vliet-Ostaptchouk J V JV
Hampel R R
Thorand B B
De Faire U U
Nyberg F F
Kuh D D
Martin N G NG
Montgomery G W GW
Heath A C AC
Madden P A F PA
Osmond C C
Pulizzi N N
Roswall N N
Halkjaer J J
Overvad K K
Uusitupa M M
Kinnunen L L
Lindström J J
Saramies J J
Keinänen-Kiukaanniemi S S
Uusitalo H H
Hussi E E
Baldassarre D D
Veglia F F
Humphries S S
Tremoli E E
Heitmann B B
JOURNAL
VOLUME: 16
ISSUE: 4
TITLE: Obesity reviews : an official journal of the International Association for the Study of Obesity
ISOABBREVIATION: Obes Rev
YEAR: 2015
MONTH: Apr
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1467-789X
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Obes Rev
COUNTRY: England
ISSNLINKING: 1467-7881
NLMUNIQUEID: 100897395
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
14136 Cancer Research UK United Kingdom
CA055075 NCI NIH HHS United States
CA134958 NCI NIH HHS United States
CA49449 NCI NIH HHS United States
CA87969 NCI NIH HHS United States
DK08014 NIDDK NIH HHS United States
DK091718 NIDDK NIH HHS United States
DK098311 NIDDK NIH HHS United States
DK46200 NIDDK NIH HHS United States
DK58845 NIDDK NIH HHS United States
DK70756 NIDDK NIH HHS United States
EY015473 NEI NIH HHS United States
G1000143 Medical Research Council United Kingdom
HL071981 NHLBI NIH HHS United States
HL073168 NHLBI NIH HHS United States
HL088521 NHLBI NIH HHS United States
HL34594 NHLBI NIH HHS United States
MC_U106179471 Medical Research Council United Kingdom
MC_UU_12013/1 Medical Research Council United Kingdom
MC_UU_12015/1 Medical Research Council United Kingdom
MC_UU_12019/1 Medical Research Council United Kingdom
MR/K013351/1 Medical Research Council United Kingdom
P30 DK046200 NIDDK NIH HHS United States
P30DK46200 NIDDK NIH HHS United States
R01 AA007535 NIAAA NIH HHS United States
R01 AA010249 NIAAA NIH HHS United States
R01 AA014041 NIAAA NIH HHS United States
R01 DK062370 NIDDK NIH HHS United States
R01 DK091718 NIDDK NIH HHS United States
U01CA137088 NCI NIH HHS United States
U01HG004399 NHGRI NIH HHS United States
U01HG004728 NHGRI NIH HHS United States
U54CA155626 NCI NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
FTO
meta-analysis
mortality
obesity
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adiposity genetics
Body Mass Index genetics
Genetic Predisposition to Disease genetics
Genetic Variation genetics
Genome-Wide Association Study genetics
Humans genetics
Obesity mortality
Observational Studies as Topic mortality
Polymorphism, Single Nucleotide mortality
Proteins genetics
Waist Circumference genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 FTO protein, human
0 Proteins
OTHER ID's
OTHERID SOURCE
NIHMS710887 NLM
PMC4564522 NLM
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