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Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk
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2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 3, p. 404-413Article in journal (Refereed) Published
Abstract [en]

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. 

Place, publisher, year, edition, pages
Nature Publishing Group, 2019. Vol. 51, no 3, p. 404-413
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Neurology
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URN: urn:nbn:se:hj:diva-43026DOI: 10.1038/s41588-018-0311-9ISI: 000459947200010PubMedID: 30617256Scopus ID: 2-s2.0-85059641255Local ID: ;HHJARNISOAI: oai:DiVA.org:hj-43026DiVA, id: diva2:1289593
Available from: 2019-02-18 Created: 2019-02-18 Last updated: 2019-03-14

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Karlsson, Ida K.

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