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Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations

Abstract

We analyzed genome-wide association data from 1,380 Europeans with early-onset and morbid adult obesity and 1,416 age-matched normal-weight controls. Thirty-eight markers showing strong association were further evaluated in 14,186 European subjects. In addition to FTO and MC4R, we detected significant association of obesity with three new risk loci in NPC1 (endosomal/lysosomal Niemann-Pick C1 gene, P = 2.9 × 10−7), near MAF (encoding the transcription factor c-MAF, P = 3.8 × 10−13) and near PTER (phosphotriesterase-related gene, P = 2.1 × 10−7).

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Acknowledgements

We thank the subjects and families who participated in this study. This work was supported by grants from the “Agence Nationale de la Recherche,” the “Conseil Regional Nord-Pas de Calais/Fonds européen de développement économique et régional,” Genome Quebec/Genome Canada and the Medical Research Council. The German cohorts and projects were supported by grants from the German Research Council (KFO152 “Atherobesity”). We thank F. Allegaert, M. Deweirder, R. Tauscher and A. Berthold for their technical support in DNA extraction and distribution. We thank P. Bougnères and C. Le Stunff for providing DNA samples of the “Saint Vincent de Paul” obese children cohort. Northern Finland Birth Cohort 1986 (NFBC1986) was supported by the European Commission; contract number QLG1-CT-2000-01643, Biocenter, University of Oulu, Finland and the Academy of Finland. We thank L. Peltonen for providing NFBC1986 DNA samples. We acknowledge the “Centre de Médecine Préventive (CMP) de Vandoeuvre les Nancy” where the STANISLAS cohort was recruited.

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Writing team: D.M., P.F., J.-C.C., A.I.F.B., M.I.M., A.W., C.D., R.S.; all others reviewed and approved the manuscript. Project management: D.M., J.D., A.W., C.D., P.F. Genome-wide association sampling and genotyping: D.M., J.D., S.L., E.D., J.T., M.M., M.T., S.V.-S., R.S., B.H., A.M., C.P., B.B. Confirmation study sampling and genotyping: D.M., J.D., E.D., V.V., A.K., P.K., W.K., J.T., M.M., A.L.H., P.E., F.H., N.P., S.H., C.L-.M., F.P., B.H., J.W., M.-R.J., B.B. Statistical analysis and informatics: D.M., C.L., S.G., F.D., C.P., S.G., L.J.M.C., J.A., D.B., C.D. Candidate gene analysis: J.C.C., D.M., S.G., F.D., S.G.

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Correspondence to Philippe Froguel.

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Meyre, D., Delplanque, J., Chèvre, JC. et al. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet 41, 157–159 (2009). https://doi.org/10.1038/ng.301

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