小柯机器人

冰岛大学Daniel F. Gudbjartsson和Kari Stefansson共同合作，近期取得重要工作进展。他们研究发现序列变体对血脂水平和冠状动脉疾病具有复杂的影响。相关研究成果2023年9月14日在线发表于《细胞》杂志上。

据介绍，许多序列变体对血脂水平具有累加效应，从而对冠状动脉疾病（CAD）风险产生累加效应。

研究结果表明，变体还具有非累加效应，并相互作用以影响血脂水平以及影响变异和共相关。变异和共相关效应通常是上位性或基因与环境相互作用的标志。这些复杂的影响可能转化为CAD风险。例如，FUT2中的第154位Trp替换位Ter可预防A1血型受试者患CAD，而其他血型受试者中患CAD的风险更大。ADH1B中的第48位组氨酸替换为精氨酸与饮酒相结合，会影响血脂水平和CAD。TM6SF2变异对血脂的影响在从不吃多脂鱼的人群中最大，而在经常吃油性鱼的人群中则没有。

总之，这一研究表明，影响数量性状变异的突变体可以发现上位效应以及变体与环境的相互作用。

附：英文全文

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

Author: Audunn S. Snaebjarnarson, Anna Helgadottir, Gudny A. Arnadottir, Erna V. Ivarsdottir, Gudmar Thorleifsson, Egil Ferkingstad, Gudmundur Einarsson, Gardar Sveinbjornsson, Thorgeir E. Thorgeirsson, Magnus O. Ulfarsson, Bjarni V. Halldorsson, Isleifur Olafsson, Christian Erikstrup, Ole B. Pedersen, Mette Nyegaard, Mie T. Bruun, Henrik Ullum, Sren Brunak, Kasper Karmark Iversen, Alex Hoerby Christensen, Morten S. Olesen, Jonas Ghouse, Karina Banasik, Kirk U. Knowlton, David O. Arnar, Gudmundur Thorgeirsson, Lincoln Nadauld, Sisse Rye Ostrowski, Henning Bundgaard, Hilma Holm, Patrick Sulem, Kari Stefansson, Daniel F. Gudbjartsson

Issue&Volume: 2023/09/14

Abstract: 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.

DOI: 10.1016/j.cell.2023.08.012

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00901-7#%20