dc.contributor.author | Desikan, Rahul S. | |
dc.contributor.author | Schork, Andrew J. | |
dc.contributor.author | Wang, Yunpeng | |
dc.contributor.author | Thompson, Wesley K. | |
dc.contributor.author | Dehghan, Abbas | |
dc.contributor.author | Ridker, Paul M. | |
dc.contributor.author | Chasman, Daniel I. | |
dc.contributor.author | McEvoy, Linda K. | |
dc.contributor.author | Holland, Dominic | |
dc.contributor.author | Chen, Chi-Hua | |
dc.contributor.author | Karow, David S. | |
dc.contributor.author | Brewer, James B. | |
dc.contributor.author | Hess, Christopher P. | |
dc.contributor.author | Williams, Julie | |
dc.contributor.author | Sims, Rebecca | |
dc.contributor.author | O'Donovan, Michael C. | |
dc.contributor.author | Choi, Seung Hoan | |
dc.contributor.author | Bis, Joshua C. | |
dc.contributor.author | Ikram, M. Arfan | |
dc.contributor.author | Gudnason, Vilmundur | |
dc.contributor.author | DeStefano, Anita L. | |
dc.contributor.author | Van Der Lee, Sven J. | |
dc.contributor.author | Psaty, Bruce M. | |
dc.contributor.author | Van Duijn, Cornelia M. | |
dc.contributor.author | Launer, Lenore | |
dc.contributor.author | Seshadri, Sudha | |
dc.contributor.author | Pericak-Vance, Margaret A. | |
dc.contributor.author | Mayeux, Richard | |
dc.contributor.author | Haines, Jonathan L. | |
dc.contributor.author | Farrer, Lindsay A. | |
dc.contributor.author | Hardy, John | |
dc.contributor.author | Ulstein, Ingun | |
dc.contributor.author | Aarsland, Dag | |
dc.contributor.author | Fladby, Tormod | |
dc.contributor.author | White, Linda | |
dc.contributor.author | Sando, Sigrid Botne | |
dc.contributor.author | Rongve, Arvid | |
dc.contributor.author | Witoelar, Aree | |
dc.contributor.author | Djurovic, Srdjan | |
dc.contributor.author | Hyman, Bradley T. | |
dc.contributor.author | Snædal, Jon | |
dc.contributor.author | Steinberg, Stacy | |
dc.contributor.author | Stefansson, Hreinn | |
dc.contributor.author | Stefánsson, Kári | |
dc.contributor.author | Schellenberg, Gerard D. | |
dc.contributor.author | Andreassen, Ole Andreas | |
dc.contributor.author | Dale, Anders | |
dc.date.accessioned | 2018-01-09T12:35:54Z | |
dc.date.available | 2018-01-09T12:35:54Z | |
dc.date.created | 2015-08-21T15:29:57Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Circulation. 2015, 131 (23), 2061-2069. | nb_NO |
dc.identifier.issn | 0009-7322 | |
dc.identifier.uri | http://hdl.handle.net/11250/2476417 | |
dc.description.abstract | Background—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 Results—Using summary statistics (P values and odds ratios) from genome-wide association studies of >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 <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=1.05–1.11; P=2.86×10−8) and chromosome 10 (rs7920721; closest gene, ECHDC3; odds ratio=1.07; 95% confidence interval=1.04–1.11; P=3.38×10−8). We also found that gene expression of HS3ST1 and ECHDC3 was altered in AD brains compared with control brains.
Conclusions—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. | nb_NO |
dc.language.iso | eng | nb_NO |
dc.publisher | American Heart Association | nb_NO |
dc.title | Polygenic overlap between C-reactive protein, plasma lipids, and Alzheimer disease | nb_NO |
dc.type | Journal article | nb_NO |
dc.type | Peer reviewed | nb_NO |
dc.description.version | acceptedVersion | nb_NO |
dc.source.pagenumber | 2061-2069 | nb_NO |
dc.source.volume | 131 | nb_NO |
dc.source.journal | Circulation | nb_NO |
dc.source.issue | 23 | nb_NO |
dc.identifier.doi | 10.1161/CIRCULATIONAHA.115.015489 | |
dc.identifier.cristin | 1259324 | |
dc.relation.project | Norges forskningsråd: 237250 | nb_NO |
dc.description.localcode | © 2015 American Heart Association, Inc. This is the authors' accepted and reviewed manuscript of the article. | nb_NO |
cristin.unitcode | 194,65,30,0 | |
cristin.unitname | Institutt for nevromedisin og bevegelsesvitenskap | |
cristin.ispublished | true | |
cristin.fulltext | postprint | |
cristin.qualitycode | 2 | |