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Heritability estimation using genetic similarity representation
时间:2025年12月20日 17:03 点击数:

报告人:王健桥

报告地点:人民大街数学与统计学院惟真楼523报告厅

报告时间:2025年12月22日星期一15:30-16:30

邀请人:郑术蓉

报告摘要:

We introduce a similarity representation framework for robust heritability estimation in Genome-Wide Association Studies (GWAS). This problem parallels the signal-to-noise ratio estimation problem in the presence of a large number of predictors in linear models. Traditional fixed and random-effects methods for heritability estimation often impose restrictive assumptions on regression coefficients or the design (genotype) matrix. These assumptions are usually violated by the heterogeneous effects of genetic variants (regression coefficients) that depend on the genotype distribution and the correlation among genotypes due to linkage disequilibrium. This leads to the non-robust estimation of heritability in practice. To overcome these limitations, we propose a SiMILarity rEpresentation method (SMILE) by modeling the dependence of the gram matrix of the outcome vector (outcome similarity) on the gram matrix of the genetic signal vector (genetic similarity). We represent the genetic similarity using a weighted gram matrix of genotypes, where a data-dependent weight matrix is used to disentangle the heterogeneous variant effects from the genotype distribution. SMILE includes the classical random-effects model as a special case and improves the fixed-effects model by not requiring accurate estimation of the precision matrix or the regression coefficients. We develop a scalable implementation for efficient analysis of large biobank GWAS data. Extensive simulations and the analysis of the UK biobank data demonstrate the robustness of the proposed method over the existing methods across a range of genetic architectures, and show that SMILE provides a versatile approach for heritability estimation.

主讲人简介:

王健桥,清华大学统计与数据科学系助理教授、博士生导师。2022年于宾夕法尼亚大学获得生物统计学博士学位,随后于2022年8月至2024年12月在美国哈佛大学生物统计系从事博士后研究。其研究聚焦于构建稳健且具可解释性的高维与超高维统计方法,并将其应用于复杂结构的大规模基因组数据分析,相关方法学成果发表于 Journal of the American Statistical Association、Biometrika 和 Annals of Applied Statistics。同时在医学健康领域,针对心血管疾病与慢性肾病与合作者开展深入的跨学科研究,综合利用大规模遗传、转录组和蛋白质组数据开展系统分析,成果发表在 New England Journal of Medicine、European Heart Journal 和 Nature Communications 等国际期刊上。

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