Polygenic overlap between C-reactive protein, plasma lipids, and Alzheimer disease

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—Usin...

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Main Authors: Desikan, Rahul S, Schork, Andrew J, Wang, Yunpeng, Thompson, Wesley K, Dehghan, Abbas, Ridker, Paul M, Chasman, Daniel I, McEvoy, Linda K, Holland, Dominic, Chen, Chi-Hua, Karow, David S, Brewer, James B, Hess, Christopher P, Williams, Julie, Sims, Rebecca, O'Donovan, Michael C, Choi, Seung Hoan, Bis, Joshua C, Ikram, M. Arfan, Gudnason, Vilmundur, DeStefano, Anita L, Van Der Lee, Sven J, Psaty, Bruce M, Van Duijn, Cornelia M, Launer, Lenore, Seshadri, Sudha, Pericak-Vance, Margaret A, Mayeux, Richard, Haines, Jonathan L, Farrer, Lindsay A, Hardy, John, Ulstein, Ingun, Aarsland, Dag, Fladby, Tormod, White, Linda, Sando, Sigrid Botne, Rongve, Arvid, Witoelar, Aree, Djurovic, Srdjan, Hyman, Bradley T, Snædal, Jon, Steinberg, Stacy, Stefansson, Hreinn, Stefánsson, Kári, Schellenberg, Gerard D, Andreassen, Ole Andreas, Dale, Anders
Format: Article
Language:English
Subjects:
Alzheimer Disease
Genome-Wide Association Study
Inflammation
lipids
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Summary: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