Hinney, Anke and Albayrak, Oezguer and Antel, Jochen and Volckmar, Anna-Lena and Sims, Rebecca and Chapman, Jade and Harold, Denise and Gerrish, Amy and Heid, Iris M. and Winkler, Thomas W. and Scherag, Andre and Wiltfang, Jens and Williams, Julie and Hebebrand, Johannes (2014) Genetic Variation at the CELF1 (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. ISSN 1552-4841, 1552-485X
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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 (p(AD) = 1.1 x 10(-08)) at the locus CELF1 is also genome-wide significant for obesity (pBMI = 7.35 x 10(-09)). (2) Four additional AD risk SNPs were nominally associated with obesity (rs17125944 at FERMT2, p(BMI) = 4.03 x 10(-05), p(BMI corr) = 2.50 x 10(-03); rs3851179 at PICALM; p(BMI) = 0.002, rs2075650 at TOMM40/APOE, p(BMI) = 0.024, rs3865444 at CD33, p(BMI) = 0.024). (3) SNPs at two of the obesity risk loci (rs4836133 downstream of ZNF608; p(AD) = 0.002 and at rs713586 downstream of RBJ/DNAJC27; p(AD) = 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 (p(AD) = 7.20 x 10(-07)), was also associated with obesity (SNP at IQCK/GPRC5B; p(BMI) = 5.21 x 10(-06); p(corr) = 3.24 x 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. (C) 2014 Wiley Periodicals, Inc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BODY-MASS INDEX; MAJOR PSYCHIATRIC-DISORDERS; APOLIPOPROTEIN-E; LATE-LIFE; METABOLIC SYNDROME; LIPID-LEVELS; RISK LOCI; COGNITIVE IMPAIRMENT; VASCULAR DEMENTIA; OLDER-ADULTS; dementia; obesity; loci; cross-disorder; shared |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Oct 2019 09:59 |
| Last Modified: | 28 Oct 2019 09:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10093 |
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