PuSH - Publikationsserver des Helmholtz Zentrums München: Variants in the <em>FTO</em> and<em> CDKAL1 </em>loci have recessive effects on risk of obesity and type 2 diabetes, respectively.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Wood, A.R.* ; Tyrrell, J.* ; Beaumont, R.* ; Jones, S.E.* ; Tuke, M.A.* ; Ruth, K.S.* ; Yaghootkar, H.* ; Freathy, R.M.* ; Murray, A.* ; Frayling, T.M.* ; Weedon, M.N.* ; GIANT Consortium (Chen, C.M. ; Gieger, C. ; Grallert, H. ; Heid, I.M. ; Heinrich, J. ; Illig, T. ; Lamina, C. ; Meitinger, T. ; Peters, A. ; Rzehak, P. ; Thiering, E. ; Wichmann, H.-E.)

Variants in the FTO and CDKAL1 loci have recessive effects on risk of obesity and type 2 diabetes, respectively.

Diabetologia 59, 1214-1221 (2016)

Verlagsversion

Forschungsdaten

DOI

	Open Access Hybrid

Abstract
Metriken
Zusatzinfos

Aims/hypothesis Genome-wide association (GWA) studies have identified hundreds of common genetic variants associated with obesity and type 2 diabetes. These studies have usually focused on additive association tests. Identifying deviations from additivity may provide new biological insights and explain some of the missing heritability for these diseases. Methods We performed a GWA study using a dominance deviation model for BMI, obesity (29,925 cases) and type 2 diabetes (4,040 cases) in 120,286 individuals of British ancestry from the UK Biobank study. We also investigated whether single nucleotide polymorphisms previously shown to be associated with these traits showed any enrichment for departures from additivity. Results Known obesity-associated variants in FTO showed strong evidence of deviation from additivity (p(DOMDEV) = 3 x 10(-5)) through a recessive effect of the allele associated with higher BMI. The average BMI of individuals carrying zero, one or two BMI-raising alleles was 27.27 (95% CI 27.22, 27.31) kg/m(2), 27.54 (95% CI 27.50, 27.58) kg/m(2) and 28.07 (95% CI 28.00, 28.14) kg/m(2), respectively. A similar effect was observed in 105,643 individuals from the GIANT Consortium (p(DOMDEV) = 0.003; meta-analysis p(DOMDEV) = 1 x 10(-7)). For type 2 diabetes, we detected a recessive effect (p(DOMDEV) = 5 x 10(-4)) at CDKAL1. Relative to homozygous non-risk allele carriers, homozygous risk allele carriers had an OR of 1.48 (95% CI 1.32, 1.65), while the heterozygous group had an OR of 1.06 (95% CI 0.99, 1.14), a result consistent with that of a previous study. We did not identify any novel associations at genome-wide significance. Conclusions/interpretation Although we found no evidence of widespread non-additive genetic effects contributing to obesity and type 2 diabetes risk, we did find robust examples of recessive effects at the FTO and CDKAL1 loci.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Scopus
Cited By

Altmetric

6.206

1.732