当前位置: X-MOL 学术Hum. Hered. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Genetic-Epigenetic Interactions in Asthma Revealed by a Genome-Wide Gene-Centric Search.
Human Heredity ( IF 1.8 ) Pub Date : 2019-01-22 , DOI: 10.1159/000489765
Vladimir Kogan 1 , Joshua Millstein 2 , Stephanie J London 3 , Carole Ober 4 , Steven R White 5 , Edward T Naureckas 5 , W James Gauderman 1 , Daniel J Jackson 6 , Albino Barraza-Villarreal 7 , Isabelle Romieu 8 , Benjamin A Raby 9 , Carrie V Breton 1
Affiliation  

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.

中文翻译:

基因组范围内的基因中心搜索揭示了哮喘的遗传表观遗传相互作用。

目的有证据表明哮喘的发病机理受遗传和表观遗传变异的独立影响,还有一些证据表明遗传表观遗传相互作用会影响哮喘的风险。然而,很少有研究来确定全基因组范围内的这种相互作用。这项研究的目的是鉴定与哮喘相关的遗传表观遗传相互作用的基因。方法使用哮喘病例对照数据,我们应用了一种新颖的以非参数基因为中心的方法,来测试整个基因组中18,178个基因附近的多个SNP和CpG位点之间的相互作用。结果十二个基因PF4,ATF3,TPRA1,HOPX,SCARNA18,STC1,OR10K1,UPK1B,LOC101928523,LHX6,CHMP4B和LANCL1具有统计上显着的SNP-CpG相互作用(错误发现率= 0。05)。其中,先前有3个涉及哮喘风险(PF4,ATF3和TPRA1)。后续分析显示,这些基因中的几个基因(包括SCARNA18,LHX6和LOC101928523)在统计学上具有显着的成对SNP-CpG相互作用(分别为p = 1.33E-04、8.21E-04、1.11E-03)。结论遗传和表观遗传变异的联合作用可能在哮喘发病中起重要作用。可能需要同时考虑整个染色体区域多个变异的统计方法,才能在全基因组范围内检测这些类型的效应。分别)。结论遗传和表观遗传变异的联合作用可能在哮喘发病中起重要作用。可能需要同时考虑整个染色体区域多个变异的统计方法,才能在全基因组范围内检测这些类型的效应。分别)。结论遗传和表观遗传变异的联合作用可能在哮喘发病中起重要作用。可能需要同时考虑整个染色体区域多个变异的统计方法,才能在全基因组范围内检测这些类型的效应。
更新日期:2019-11-01
down
wechat
bug