Genetic-Epigenetic Interactions in Asthma Revealed by a Genome-Wide Gene-Centric Search.

IF 1.1 4区生物学 Q4 GENETICS & HEREDITY Human Heredity Pub Date : 2018-01-01 Epub Date: 2019-01-22 DOI:10.1159/000489765

Vladimir Kogan, Joshua Millstein, Stephanie J London, Carole Ober, Steven R White, Edward T Naureckas, W James Gauderman, Daniel J Jackson, Albino Barraza-Villarreal, Isabelle Romieu, Benjamin A Raby, Carrie V Breton

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Abstract

Objectives: There is evidence to suggest that asthma pathogenesis is affected by both genetic and epigenetic variation independently, and there is some evidence to suggest that genetic-epigenetic interactions affect risk of asthma. However, little research has been done to identify such interactions on a genome-wide scale. The aim of this studies was to identify genes with genetic-epigenetic interactions associated with asthma.

Methods: Using asthma case-control data, we applied a novel nonparametric gene-centric approach to test for interactions between multiple SNPs and CpG sites simultaneously in the vicinities of 18,178 genes across the genome.

Results: Twelve genes, PF4, ATF3, TPRA1, HOPX, SCARNA18, STC1, OR10K1, UPK1B, LOC101928523, LHX6, CHMP4B, and LANCL1, exhibited statistically significant SNP-CpG interactions (false discovery rate = 0.05). Of these, three have previously been implicated in asthma risk (PF4, ATF3, and TPRA1). Follow-up analysis revealed statistically significant pairwise SNP-CpG interactions for several of these genes, including SCARNA18, LHX6, and LOC101928523 (p = 1.33E-04, 8.21E-04, 1.11E-03, respectively).

Conclusions: Joint effects of genetic and epigenetic variation may play an important role in asthma pathogenesis. Statistical methods that simultaneously account for multiple variations across chromosomal regions may be needed to detect these types of effects on a genome-wide scale.

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以基因组为中心的全基因组搜索揭示了哮喘中基因与表观遗传学的相互作用

目的：有证据表明，哮喘的发病机制受到遗传和表观遗传变异的独立影响，也有证据表明，遗传与表观遗传之间的相互作用会影响哮喘的发病风险。然而，在全基因组范围内确定这种相互作用的研究却很少。本研究旨在确定与哮喘相关的遗传-表观遗传相互作用基因：方法：我们利用哮喘病例对照数据，采用一种新颖的非参数基因中心方法，在全基因组的 18,178 个基因附近同时检测多个 SNP 与 CpG 位点之间的相互作用：结果发现：PF4、ATF3、TPRA1、HOPX、SCARNA18、STC1、OR10K1、UPK1B、LOC101928523、LHX6、CHMP4B 和 LANCL1 这 12 个基因表现出具有统计学意义的 SNP-CpG 相互作用（假发现率 = 0.05）。其中，3 个 SNP 与哮喘风险有关（PF4、ATF3 和 TPRA1）。后续分析表明，其中几个基因，包括 SCARNA18、LHX6 和 LOC101928523 的 SNP-CpG 成对相互作用具有统计学意义（p = 1.33E-04、8.21E-04、1.11E-03）：遗传和表观遗传变异的联合效应可能在哮喘发病机制中发挥重要作用。结论：遗传和表观遗传变异的联合效应可能在哮喘发病机制中发挥重要作用。要在全基因组范围内检测这类效应，可能需要同时考虑染色体区域多重变异的统计方法。

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

Human Heredity 生物-遗传学

CiteScore

2.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Gathering original research reports and short communications from all over the world, ''Human Heredity'' is devoted to methodological and applied research on the genetics of human populations, association and linkage analysis, genetic mechanisms of disease, and new methods for statistical genetics, for example, analysis of rare variants and results from next generation sequencing. The value of this information to many branches of medicine is shown by the number of citations the journal receives in fields ranging from immunology and hematology to epidemiology and public health planning, and the fact that at least 50% of all ''Human Heredity'' papers are still cited more than 8 years after publication (according to ISI Journal Citation Reports). Special issues on methodological topics (such as ‘Consanguinity and Genomics’ in 2014; ‘Analyzing Rare Variants in Complex Diseases’ in 2012) or reviews of advances in particular fields (‘Genetic Diversity in European Populations: Evolutionary Evidence and Medical Implications’ in 2014; ‘Genes and the Environment in Obesity’ in 2013) are published every year. Renowned experts in the field are invited to contribute to these special issues.