PWAS Hub: exploring gene-based associations of complex diseases with sex dependency

IF 16.6 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Nucleic Acids Research Pub Date : 2024-11-20 DOI:10.1093/nar/gkae1125

Roei Zucker, Guy Kelman, Michal Linial

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Abstract

The Proteome-Wide Association Study (PWAS) is a protein-based genetic association approach designed to complement traditional variant-based methods like GWAS. PWAS operates in two stages: first, machine learning models predict the impact of genetic variants on protein-coding genes, generating effect scores. These scores are then aggregated into a gene-damaging score for each individual. This score is then used in case-control statistical tests to significantly link to specific phenotypes. PWAS Hub (v1.2) is a user-friendly platform that facilitates the exploration of gene-disease associations using clinical and genetic data from the UK Biobank (UKB), encompassing 500k individuals. PWAS Hub reports on 819 diseases and phenotypes determined by PheCode and ICD-10 clinical codes, each with a minimum of 400 affected individuals. PWAS-derived gene associations were reported for 72% of the tested phenotypes. The PWAS Hub also analyzes gene associations separately for males and females, considering sex-specific genetic effects, inheritance patterns (dominant and recessive), and gene pleiotropy. We illustrated the utility of the PWAS Hub for primary (essential) hypertension (I10), type 2 diabetes mellitus (E11), and specified haematuria (R31) that showed sex-dependent genetic signals. The PWAS Hub, available at pwas.huji.ac.il, is a valuable resource for studying genetic contributions to common diseases and sex-specific effects.

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PWAS Hub：探索复杂疾病与性依赖的基因关联

全蛋白质组关联研究（PWAS）是一种基于蛋白质的遗传关联方法，旨在对基于变异的传统方法（如全球基因组分析）进行补充。PWAS 分两个阶段运行：首先，机器学习模型预测遗传变异对蛋白编码基因的影响，生成效应得分。然后将这些分数汇总为每个个体的基因损害分数。然后将该分数用于病例对照统计测试，以确定其与特定表型的显著联系。PWAS Hub（v1.2）是一个用户友好型平台，可利用英国生物库（UKB）的临床和遗传数据（包括 50 万个个体）帮助探索基因与疾病的关联。PWAS 中枢报告了由 PheCode 和 ICD-10 临床代码确定的 819 种疾病和表型，每种疾病和表型至少有 400 个受影响的个体。72% 的测试表型报告了 PWAS 衍生基因关联。PWAS 中枢还能分别分析男性和女性的基因关联，并考虑到性别特异性遗传效应、遗传模式（显性和隐性）以及基因多效性。我们展示了 PWAS Hub 在原发性（本质）高血压（I10）、2 型糖尿病（E11）和特定血尿（R31）方面的实用性，这些疾病都显示出性别依赖性遗传信号。PWAS中枢可在pwas.huji.ac.il上查阅，是研究常见疾病遗传贡献和性别特异性影响的宝贵资源。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nucleic Acids Research 生物-生化与分子生物学

CiteScore

27.10

自引率

4.70%

发文量

1057

审稿时长

2 months

期刊介绍： Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.