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Genetic variation at the CELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity

Authors

  • Anke Hinney,

    Corresponding author
    1. Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany
    • Correspondence to:

      Anke Hinney, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Universitätsklinikum Essen, University of Duisburg-Essen, Virchowstr. 171, D-45147 Essen, Germany.

      E-mail: anke.hinney@uni-due.de

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  • Özgür Albayrak,

    1. Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany
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  • Jochen Antel,

    1. Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany
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  • Anna-Lena Volckmar,

    1. Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany
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  • Rebecca Sims,

    1. Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Heath Park, Cardiff, UK
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  • Jade Chapman,

    1. Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Heath Park, Cardiff, UK
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  • Denise Harold,

    1. Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Heath Park, Cardiff, UK
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  • Amy Gerrish,

    1. Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Heath Park, Cardiff, UK
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  • Iris M. Heid,

    1. Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
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  • Thomas W. Winkler,

    1. Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
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  • André Scherag,

    1. Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany
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  • Jens Wiltfang,

    1. Department of Psychiatry and Psychotherapy, Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany
    2. Psychiatrische Klinik, Universitätsklinikum Göttingen, Göttingen, Germany
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  • Julie Williams,

    1. Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Heath Park, Cardiff, UK
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  • Johannes Hebebrand,

    1. Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany
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  • GERAD Consortium,

    1. GERAD (Genetic and Environmental Risk for Alzheimer's Disease) Consortium
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    • Data used in the preparation of this article were obtained from the Genetic and Environmental Risk for Alzheimer's disease (GERAD1) Consortium and from the IGAP Consortium. As such, the investigators within the GERAD1 consortia contributed to the design and implementation of GERAD1 and/or provided data but did not participate in analysis or writing of this report. The full list of collaborators can be found in the supplementary material.
  • IGAP Consortium,

    1. IGAP (International Genomics of Alzheimer's Project Consortium) Consortium
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    • Data used in the preparation of this article were obtained from the Genetic and Environmental Risk for Alzheimer's disease (GERAD1) Consortium and from the IGAP Consortium. As such, the investigators within the GERAD1 consortia contributed to the design and implementation of GERAD1 and/or provided data but did not participate in analysis or writing of this report. The full list of collaborators can be found in the supplementary material.
  • GIANT Consortium

    1. GIANT (Genetic Investigation of ANthropometric Traits) Consortium
    Search for more papers by this author
    • Data used in the preparation of this article were obtained from the Genetic and Environmental Risk for Alzheimer's disease (GERAD1) Consortium and from the IGAP Consortium. As such, the investigators within the GERAD1 consortia contributed to the design and implementation of GERAD1 and/or provided data but did not participate in analysis or writing of this report. The full list of collaborators can be found in the supplementary material.

  • Conflict of interest: The authors declare no conflict of interest.

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. © 2014 Wiley Periodicals, Inc.

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