| Literature DB >> 31272697 |
Jeremy A Elman1, Matthew S Panizzon2, Mark W Logue3, Nathan A Gillespie4, Michael C Neale4, Chandra A Reynolds5, Daniel E Gustavson2, Brinda K Rana2, Ole A Andreassen6, Anders M Dale7, Carol E Franz2, Michael J Lyons8, William S Kremen9.
Abstract
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.Entities:
Keywords: Alzheimer's disease; Cognitive impairment; Coronary artery disease; Incidence-prevalence bias; Neyman bias; Polygenic risk scores
Year: 2019 PMID： 31272697 PMCID： PMC6899214 DOI： 10.1016/j.neurobiolaging.2019.06.001
Source DB: PubMed Journal: Neurobiol Aging ISSN： 0197-4580 Impact factor: 4.673