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Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk
- Jansen, I. E. (author)
- Savage, J. E. (author)
- Watanabe, K. (author)
- show more...
- Sealock, J. (author)
- Hägg, S. (author)
- Athanasiu, L. (author)
- Voyle, N. (author)
- Witoelar, A. (author)
- Stringer, S. (author)
- Almdahl, I. S. (author)
- Andersen, F. (author)
- Bergh, S. (author)
- Bettella, F. (author)
- Bjornsson, S. (author)
- Brækhus, A. (author)
- Bråthen, G. (author)
- de Leeuw, C. (author)
- Desikan, R. S. (author)
- Djurovic, S. (author)
- Dumitrescu, L. (author)
- Fladby, T. (author)
- Hohman, T. J. (author)
- Jonsson, P. V. (author)
- Kiddle, S. J. (author)
- Rongve, A. (author)
- Saltvedt, I. (author)
- Sando, S. B. (author)
- Selbæk, G. (author)
- Shoai, M. (author)
- Skene, N. G. (author)
- Snaedal, J. (author)
- Stordal, E. (author)
- Ulstein, I. D. (author)
- Wang, Y. (author)
- White, L. R. (author)
- Hardy, J. (author)
- Sullivan, P. F. (author)
- van der Flier, W. M. (author)
- Dobson, R. (author)
- Davis, L. K. (author)
- Stefansson, H. (author)
- Stefansson, K. (author)
- Ripke, S. (author)
- Andreassen, O. A. (author)
- Posthuma, D. (author)
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- (creator_code:org_t)
- 2019-01-07
- 2019
- English.
- In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 404-413
- Journal article (peer-reviewed)
Abstract
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- Alzheimer’s disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (rg = 0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver, and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomization results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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- art (subject category)
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- By the author/editor
- Jansen, I. E.
- Savage, J. E.
- Watanabe, K.
- Bryois, J.
- Williams, D. M.
- Steinberg, S.
- show more...
- Sealock, J.
- Karlsson, Ida K.
- Hägg, S.
- Athanasiu, L.
- Voyle, N.
- Proitsi, P.
- Witoelar, A.
- Stringer, S.
- Aarsland, D.
- Almdahl, I. S.
- Andersen, F.
- Bergh, S.
- Bettella, F.
- Bjornsson, S.
- Brækhus, A.
- Bråthen, G.
- de Leeuw, C.
- Desikan, R. S.
- Djurovic, S.
- Dumitrescu, L.
- Fladby, T.
- Hohman, T. J.
- Jonsson, P. V.
- Kiddle, S. J.
- Rongve, A.
- Saltvedt, I.
- Sando, S. B.
- Selbæk, G.
- Shoai, M.
- Skene, N. G.
- Snaedal, J.
- Stordal, E.
- Ulstein, I. D.
- Wang, Y.
- White, L. R.
- Hardy, J.
- Hjerling-Leffler ...
- Sullivan, P. F.
- van der Flier, W ...
- Dobson, R.
- Davis, L. K.
- Stefansson, H.
- Stefansson, K.
- Pedersen, N. L.
- Ripke, S.
- Andreassen, O. A ...
- Posthuma, D.
- show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Clinical Medicin ...
- and Neurology
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- Nature Genetics
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- Jönköping University
- Karolinska Institutet
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