PuSH - Publication Server of Helmholtz Zentrum München: Genetic predisposition to weight loss and regain with lifestyle intervention: Analyses from the Diabetes Prevention Program and the Look AHEAD randomized controlled trials.

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Papandonatos, G.D.* ; Pan, Q.* ; Pajewski, N.M.* ; Delahanty, L.M.* ; Peter, I.* ; Erar, B.* ; Ahmad, S.* ; Harden, M.* ; Chen, L.* ; Fontanillas, P.* ; GIANT Consortium (Albrecht, E. ; Gieger, C. ; Grallert, H. ; Heid, I.M. ; Illig, T. ; Müller-Nurasyid, M. ; Peters, A. ; Thorand, B. ; Wichmann, H.-E.) ; Wagenknecht, L.E.* ; Kahn, S.E.* ; Wing, R.R.* ; Jablonski, K.A.* ; Huggins, G.S.* ; Knowler, W.C.* ; Florez, J.C* ; McCaffery, J.M.* ; Franks, P.W.* ; Diabetes Prevention Program (*) ; Look AHEAD Research Group (*)

Genetic predisposition to weight loss and regain with lifestyle intervention: Analyses from the Diabetes Prevention Program and the Look AHEAD randomized controlled trials.

Diabetes 64, 4312-4321 (2015)

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We investigated the genetic overlap between Alzheimer’s disease (AD) and Parkinson’s disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10⁻⁷). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer’s neurodegeneration.

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