Genetic risk for coronary heart disease alters the influence of Alzheimer's genetic risk on mild cognitive impairment

NEUROBIOLOGY OF AGING

卷:84

Article

Elman, Jeremy A.^1,2  Panizzon, Matthew S.^1,2  Logue, Mark W.^3,4,5,6  Gillespie, Nathan A.⁷  Neale, Michael C.⁷  Reynolds, Chandra A.⁸  Gustavson, Daniel E.^1,2  Rana, Brinda K.^1,2  Andreassen, Ole A.^9,10  Dale, Anders M.^2,11,12  Franz, Carol E.^1,2  Lyons, Michael J.¹³  Kremen, William S.^1,2,14 

[1] Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,MC 0738, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Ctr Behav Genet Aging, La Jolla, CA 92093 USA

[3] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA

[4] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA

[5] Boston Univ, Sch Med, Biomed Genet Sect, Boston, MA 02118 USA

[6] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[7] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA

[8] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA

[9] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, NORMENT, Oslo, Norway

[10] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway

[11] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA

[12] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[13] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA

[14] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, La Jolla, CA USA

关键词: Alzheimer's disease;    Coronary artery disease;    Polygenic risk scores;    Incidence-prevalence bias;    Neyman bias;    Cognitive impairment;   

DOI  :  10.1016/j.neurobiolaging.2019.06.001

来源: Elsevier

【 摘 要 】

Understanding genetic influences on Alzheimer's disease (AD) may improve early identification. AD polygenic risk scores (AD-PRSs) are associated with increased odds of AD and mild cognitive impairment (MCI). Additional sources of genetic risk may also contribute to disease outcomes. Coronary artery disease (CAD) is a risk factor for AD, interacts with AD pathology, and is also heritable. We showed that incidence-based and prevalence-based CAD-PRSs moderate the association between the AD-PRS and MCI, but in opposing directions. Higher incidence-based CAD-PRSs interacted with the AD-PRS to further increase MCI risk. Conversely, the AD-PRS was predictive of MCI when prevalence-based CAD-PRSs were low. The latter finding is likely due to prevalent CAD cases being biased toward longer postevent survival times, perhaps selecting for protective loci that offset AD risk. These results demonstrate (1) the importance of examining multiple PRSs and their interactions; (2) how genetic risk for one disease can modify the impact of genetic risk for another; and (3) the importance of considering ascertainment procedures of GWAS used for genetic risk prediction. (C) 2019 Elsevier Inc. All rights reserved.

【 授权许可】

Free