Rxivist logo

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 459 times
  • Download rankings, all-time:
    • Site-wide: 39,072 out of 100,621
    • In genomics: 3,663 out of 6,233
  • Year to date:
    • Site-wide: 46,571 out of 100,621
  • Since beginning of last month:
    • Site-wide: 27,160 out of 100,621

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


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


  • 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
  • 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
  • 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
  • 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
  • 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
  • 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
  • 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
  • 22 Jan 2019: Nature just published an article about Rxivist and our data.
  • 13 Jan 2019: The Rxivist preprint is live!