Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,591 bioRxiv papers from 298,050 authors.

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

By Jeremy A. Elman, Matthew S. Panizzon, Mark W Logue, Nathan A. Gillespie, Michael C Neale, Chandra A Reynolds, Daniel E Gustavson, Ole A. Andreassen, Anders M Dale, Carol E. Franz, Michael J Lyons, William S. Kremen

Posted 03 Oct 2018
bioRxiv DOI: 10.1101/432443 (published DOI: 10.1016/j.neurobiolaging.2019.06.001)

BACKGROUND: Alzheimer's disease (AD) is under considerable genetic influence. However, known susceptibility loci only explain a modest proportion of variance in disease outcomes. This small proportion could occur if the etiology of AD is heterogeneous. We previously found that an AD polygenic risk score (PRS) was significantly associated with mild cognitive impairment (MCI), an early stage of AD. Poor cardiovascular health is also associated with increased risk for AD and has been found to interact with AD pathology. Conditions such as coronary artery disease (CAD) are also heritable, and may contribute to heterogeneity if there are interactions of genetic risk for these conditions as there is phenotypically. However, case-control designs based on prevalent cases of a disease with relatively high case-fatality rate such as CAD may be biased toward individuals who have long post-event survival times and may therefore also identify loci with protective effects. METHODS: We compared interactions between an AD-PRS and two CAD-PRSs, one based on a GWAS of incident cases and one on prevalent cases, on MCI status in 1,209 individuals. RESULTS: As expected, the incidence-based CAD-PRS interacts with the AD-PRS to further increase MCI risk. Conversely, higher prevalence-based CAD-PRSs reduced the effect of AD genetic risk on MCI status. CONCLUSIONS: These results demonstrate: i) the utility of including multiple PRSs and their interaction effects; ii) how genetic risk for one disease may modify the impact of genetic risk for another; and iii) the importance of considering ascertainment procedures of GWAS being used for genetic risk prediction.

Download data

  • Downloaded 329 times
  • Download rankings, all-time:
    • Site-wide: 33,710 out of 67,594
    • In genomics: 3,210 out of 4,581
  • Year to date:
    • Site-wide: 23,309 out of 67,594
  • Since beginning of last month:
    • Site-wide: 26,419 out of 67,594

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News