Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics.
Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics.
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DOI：
10.3390/jpm11010059
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发表时间：
2021-01-19
影响因子：
--
通讯作者：
Wu AC
中科院分区：
文献类型：
--
作者：
Voorhies K;Sordillo JE;McGeachie M;Ampleford E;Wang AL;Lasky-Su J;Tantisira K;Dahlin A;Kelly RS;Ortega VE;Lutz SM;Wu AC
一个尚未解决的重要问题是年龄在调节哮喘患者对短效β2受体激动剂反应中的作用。本研究的目的是确定年龄是否改变单核苷酸多态性（SNP）与β2受体激动剂支气管扩张剂反应（BDR）的遗传关联。使用三个队列，共892名受试者，我们对每个队列进行了全基因组相互作用研究（GWIS），以检查SNP与BDR的年龄相互作用。采用固定效应荟萃分析对结果进行联合收割机合并。为了确定先前鉴定的BDR SNPs是否具有年龄相互作用，我们还检查了来自两个已发表的BDR全基因组关联研究（GWAS）的候选基因中的16个多态性。使用5 × 10−8的全基因组显著性水平，在BDR上没有显著的SNP与年龄的相互作用。使用5 × 10−6的提示性显著性水平，三种相互作用（包括PRAG1内的SNP（rs4840337））是显著的，并在0.05的显著性水平下重复。考虑到来自BDR的两个先前GWAS的候选基因，三个SNP（rs10476900（接近ADRB 2）[p值= 0.009]、rs10827492（CREM）[p值= 0.02]和rs72646209（NCOA 3）[p值= 0.02]）在BDR上与年龄具有轻微显著的相互作用（p < 0.05）。我们的研究结果表明，年龄可能是一个重要的修改器的遗传协会的BDR哮喘。
An unaddressed and important issue is the role age plays in modulating response to short acting β2-agonists in individuals with asthma. The objective of this study was to identify whether age modifies genetic associations of single nucleotide polymorphisms (SNPs) with bronchodilator response (BDR) to β2-agonists. Using three cohorts with a total of 892 subjects, we ran a genome wide interaction study (GWIS) for each cohort to examine SNP by age interactions with BDR. A fixed effect meta-analysis was used to combine the results. In order to determine if previously identified BDR SNPs had an age interaction, we also examined 16 polymorphisms in candidate genes from two published genome wide association studies (GWAS) of BDR. There were no significant SNP by age interactions on BDR using the genome wide significance level of 5 × 10−8. Using a suggestive significance level of 5 × 10−6, three interactions, including one for a SNP within PRAG1 (rs4840337), were significant and replicated at the significance level of 0.05. Considering candidate genes from two previous GWAS of BDR, three SNPs (rs10476900 (near ADRB2) [p-value = 0.009], rs10827492 (CREM) [p-value = 0.02], and rs72646209 (NCOA3) [p-value = 0.02]) had a marginally significant interaction with age on BDR (p < 0.05). Our results suggest age may be an important modifier of genetic associations for BDR in asthma.
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影响因子：
4.7
作者：
Amare AT;Schubert KO;Tekola-Ayele F;Hsu YH;Sangkuhl K;Jenkins G;Whaley RM;Barman P;Batzler A;Altman RB;Arolt V;Brockmöller J;Chen CH;Domschke K;Hall-Flavin DK;Hong CJ;Illi A;Ji Y;Kampman O;Kinoshita T;Leinonen E;Liou YJ;Mushiroda T;Nonen S;Skime MK;Wang L;Kato M;Liu YL;Praphanphoj V;Stingl JC;Bobo WV;Tsai SJ;Kubo M;Klein TE;Weinshilboum RM;Biernacka JM;Baune BT
通讯作者：
Baune BT
影响因子：
4.5
作者：
Himes BE;Jiang X;Hu R;Wu AC;Lasky-Su JA;Klanderman BJ;Ziniti J;Senter-Sylvia J;Lima JJ;Irvin CG;Peters SP;Meyers DA;Bleecker ER;Kubo M;Tamari M;Nakamura Y;Szefler SJ;Lemanske RF Jr;Zeiger RS;Strunk RC;Martinez FD;Hanrahan JP;Koppelman GH;Postma DS;Nieuwenhuis MA;Vonk JM;Panettieri RA Jr;Markezich A;Israel E;Carey VJ;Tantisira KG;Litonjua AA;Lu Q;Weiss ST
通讯作者：
Weiss ST
影响因子：
6.7
作者：
Drazen, JM;Silverman, EK;Lee, TH
通讯作者：
Lee, TH
影响因子：
14.2
作者：
Zeiger, RS;Szefler, SJ;Taussig, LM
通讯作者：
Taussig, LM
DOI：
10.1093/bioinformatics/btq340
发表时间：
2010-09-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Willer CJ;Li Y;Abecasis GR
通讯作者：
Abecasis GR