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dc.contributor.authorDesikan, Rahul S.
dc.contributor.authorSchork, Andrew J.
dc.contributor.authorWang, Yunpeng
dc.contributor.authorThompson, Wesley K.
dc.contributor.authorDehghan, Abbas
dc.contributor.authorRidker, Paul M.
dc.contributor.authorChasman, Daniel I.
dc.contributor.authorMcEvoy, Linda K.
dc.contributor.authorHolland, Dominic
dc.contributor.authorChen, Chi-Hua
dc.contributor.authorKarow, David S.
dc.contributor.authorBrewer, James B.
dc.contributor.authorHess, Christopher P.
dc.contributor.authorWilliams, Julie
dc.contributor.authorSims, Rebecca
dc.contributor.authorO'Donovan, Michael C.
dc.contributor.authorChoi, Seung Hoan
dc.contributor.authorBis, Joshua C.
dc.contributor.authorIkram, M. Arfan
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorDeStefano, Anita L.
dc.contributor.authorVan Der Lee, Sven J.
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorVan Duijn, Cornelia M.
dc.contributor.authorLauner, Lenore
dc.contributor.authorSeshadri, Sudha
dc.contributor.authorPericak-Vance, Margaret A.
dc.contributor.authorMayeux, Richard
dc.contributor.authorHaines, Jonathan L.
dc.contributor.authorFarrer, Lindsay A.
dc.contributor.authorHardy, John
dc.contributor.authorUlstein, Ingun
dc.contributor.authorAarsland, Dag
dc.contributor.authorFladby, Tormod
dc.contributor.authorWhite, Linda
dc.contributor.authorSando, Sigrid Botne
dc.contributor.authorRongve, Arvid
dc.contributor.authorWitoelar, Aree
dc.contributor.authorDjurovic, Srdjan
dc.contributor.authorHyman, Bradley T.
dc.contributor.authorSnædal, Jon
dc.contributor.authorSteinberg, Stacy
dc.contributor.authorStefansson, Hreinn
dc.contributor.authorStefánsson, Kári
dc.contributor.authorSchellenberg, Gerard D.
dc.contributor.authorAndreassen, Ole Andreas
dc.contributor.authorDale, Anders
dc.date.accessioned2018-02-13T13:51:31Z
dc.date.available2018-02-13T13:51:31Z
dc.date.issued2015-06
dc.identifier.citationDesikan RS, Schork AJ, Wang Y, Thompson WK, Dehghan A, Ridker PM, Chasman DI, McEvoy LK, Holland D, Chen C, Karow, Brewer JB, Hess CP, Williams, Sims, O'Donovan MC, Choi, Bis JC, Ikram MA, Gudnason V, DeStefano, Van Der Lee, Psaty BM, Van Duijn, Launer, Seshadri S, Pericak-Vance MA, Mayeux, Haines JL, Farrer, Hardy J, Ulstein I, Aarsland D, Fladby T, White LR, Sando SB, Rongve A, Witoelar AW, Djurovic S, Hyman BT, Snædal J, Steinberg S, Stefansson H, Stefánsson K, Schellenberg, Andreassen OA, Dale A. Polygenic overlap between C-reactive protein, plasma lipids, and Alzheimer disease. Circulation. 2015;131(23):2061-2069eng
dc.identifier.urihttp://hdl.handle.net/1956/17389
dc.description.abstract<p>Background&mdash;Epidemiological findings suggest a relationship between Alzheimer disease (AD), inflammation, and dyslipidemia, although the nature of this relationship is not well understood. We investigated whether this phenotypic association arises from a shared genetic basis. Methods and</p> <p>Results&mdash;Using summary statistics (P values and odds ratios) from genome-wide association studies of &gt;200 000 individuals, we investigated overlap in single-nucleotide polymorphisms associated with clinically diagnosed AD and C-reactive protein (CRP), triglycerides, and high- and low-density lipoprotein levels. We found up to 50-fold enrichment of AD single-nucleotide polymorphisms for different levels of association with C-reactive protein, low-density lipoprotein, high-density lipoprotein, and triglyceride single-nucleotide polymorphisms using a false discovery rate threshold &lt;0.05. By conditioning on polymorphisms associated with the 4 phenotypes, we identified 55 loci associated with increased AD risk. We then conducted a meta-analysis of these 55 variants across 4 independent AD cohorts (total: n=29 054 AD cases and 114 824 healthy controls) and discovered 2 genome-wide significant variants on chromosome 4 (rs13113697; closest gene, HS3ST1; odds ratio=1.07; 95% confidence interval=1.05&ndash;1.11; P=2.86&times;10&minus;8) and chromosome 10 (rs7920721; closest gene, ECHDC3; odds ratio=1.07; 95% confidence interval=1.04&ndash;1.11; P=3.38&times;10&minus;8). We also found that gene expression of HS3ST1 and ECHDC3 was altered in AD brains compared with control brains.</p> <p>Conclusions&mdash;We demonstrate genetic overlap between AD, C-reactive protein, and plasma lipids. By conditioning on the genetic association with the cardiovascular phenotypes, we identify novel AD susceptibility loci, including 2 genome-wide significant variants conferring increased risk for AD.</p>eng
dc.language.isoengeng
dc.publisherAmerican Heart Association, Inc.eng
dc.subjectAlzheimer Diseaseeng
dc.subjectGenome-Wide Association Studyeng
dc.subjectinflammationeng
dc.subjectlipidseng
dc.titlePolygenic overlap between C-reactive protein, plasma lipids, and Alzheimer diseaseeng
dc.typeJournal articleeng
dc.date.updated2018-01-04T07:29:01Z
dc.rights.holderCopyright 2015 American Heart Association, Inc.eng
dc.type.versionacceptedVersioneng
bora.peerreviewedPeer reviewedeng
dc.type.documentJournal article
dc.identifier.cristinID1259324
dc.identifier.doi10.1161/CIRCULATIONAHA.115.015489eng
dc.source.issn0009-7322eng
dc.source.issn1524-4539eng
dc.relation.projectIDNorges forskningsråd: 237250
dc.relation.journalCirculation


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