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Genetic variation at theCELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity

Hinney, Anke, Albayrak, Özgür, Antel, Jochen, Volckmar, Anna-Lena, Sims, Rebecca, Chapman, Jade, Harold, Denise, Gerrish, Amy, Heid, Iris M., Winkler, Thomas W., Scherag, André, Wiltfang, Jens, Williams, Julie and Hebebrand, Johannes 2014. Genetic variation at theCELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 165 (4) , pp. 283-293. 10.1002/ajmg.b.32234

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Abstract

Deviations from normal body weight are observed prior to and after the onset of Alzheimer's disease (AD). Midlife obesity confers increased AD risk in later life, whereas late-life obesity is associated with decreased AD risk. The role of underweight and weight loss for AD risk is controversial. Based on the hypothesis of shared genetic variants for both obesity and AD, we analyzed the variants identified for AD or obesity from genome-wide association meta-analyses of the GERAD (AD, cases = 6,688, controls = 13,685) and GIANT (body mass index [BMI] as measure of obesity, n = 123,865) consortia. Our cross-disorder analysis of genome-wide significant 39 obesity SNPs and 23 AD SNPs in these two large data sets revealed that: (1) The AD SNP rs10838725 (pAD  = 1.1 × 10(-08)) at the locus CELF1 is also genome-wide significant for obesity (pBMI  = 7.35 × 10(-09) ). (2) Four additional AD risk SNPs were nominally associated with obesity (rs17125944 at FERMT2, pBMI  = 4.03 × 10(-05), pBMI corr  = 2.50 × 10(-03) ; rs3851179 at PICALM; pBMI  = 0.002, rs2075650 at TOMM40/APOE, pBMI  = 0.024, rs3865444 at CD33, pBMI  = 0.024). (3) SNPs at two of the obesity risk loci (rs4836133 downstream of ZNF608; pAD  = 0.002 and at rs713586 downstream of RBJ/DNAJC27; pAD  = 0.018) were nominally associated with AD risk. Additionally, among the SNPs used for confirmation in both studies the AD risk allele of rs1858973, with an AD association just below genome-wide significance (pAD  = 7.20 × 10(-07)), was also associated with obesity (SNP at IQCK/GPRC5B; pBMI  = 5.21 × 10(-06) ; pcorr  = 3.24 × 10(-04)). Our first GWAS based cross-disorder analysis for AD and obesity suggests that rs10838725 at the locus CELF1 might be relevant for both disorders.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Wiley-Blackwell
ISSN: 1552-4841
Last Modified: 14 Mar 2019 11:52
URI: http://orca.cf.ac.uk/id/eprint/74908

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