Complex effects of sequence variants on lipid levels and coronary artery disease

Research output: Contribution to journalJournal articlepeer-review

Many sequence variants have additive effects on blood lipid levels and, through that, on the risk of coronary artery disease (CAD). We show that variants also have non-additive effects and interact to affect lipid levels as well as affecting variance and correlations. Variance and correlation effects are often signatures of epistasis or gene-environmental interactions. These complex effects can translate into CAD risk. For example, Trp154Ter in FUT2 protects against CAD among subjects with the A1 blood group, whereas it associates with greater risk of CAD in others. His48Arg in ADH1B interacts with alcohol consumption to affect lipid levels and CAD. The effect of variants in TM6SF2 on blood lipids is greatest among those who never eat oily fish but absent from those who often do. This work demonstrates that variants that affect variance of quantitative traits can allow for the discovery of epistasis and interactions of variants with the environment.

Original languageEnglish
JournalCell
Volume186
Issue number19
Pages (from-to)4085-4099.e15
ISSN0092-8674
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.

    Research areas

  • blood lipids, cholesterol, coronary artery disease, correlation effects, dominance effects, epistasis, gene-environment interaction effects, gene-gene interaction effects, genome-wide association study, variance effects

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