Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study.
Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study.
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DOI：
10.1186/s12931-018-0890-0
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发表时间：
2018-10-29
影响因子：
5.8
通讯作者：
COPDGene Investigators
中科院分区：
文献类型：
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作者：
Hayden LP;Cho MH;Raby BA;Beaty TH;Silverman EK;Hersh CP;COPDGene Investigators
儿童哮喘受遗传影响很大，是成人肺功能下降和慢性阻塞性肺病 (COPD) 的危险因素。本研究调查了 COPDGene 研究中成年吸烟者自我报告的儿童哮喘情况。我们假设儿童哮喘与肺功能下降、慢性阻塞性肺病风险增加有关，并且全基因组关联研究 (GWAS) 将显示与已确定的哮喘变异的关联。我们评估了年龄在 45-80 岁的非西班牙裔白人 (NHW) 或非裔美国人 (AA) 种族中当前和以前的吸烟者。儿童哮喘的定义是由医学专业人士诊断的哮喘自我报告，发病时间< 16岁或儿童时期。根据肺功能、慢性阻塞性肺病的发展和遗传变异，将有儿童哮喘病史的受试者与从未患过哮喘的受试者进行比较。 GWAS 在 NHW 和 AA 人群中进行，并合并进行荟萃分析。检查已发表文献中的两组已确定的哮喘 SNP 与儿童哮喘的关联。在 10,199 名成年吸烟者中，730 人（7%）报告有儿童哮喘病史，7493 人（73%）报告没有哮喘病史。儿童哮喘患者肺功能下降，COPD 风险增加（OR 3.42，95% CI 2.81–4.18）。对 8031 名受试者的基因型数据进行了评估。在 NHW 中，391 人（7%）患有儿童哮喘，GWAS 在 KIAA1958 中发现了一个全基因组显着关联（rs59289606，p = 4.82 × 10− 8）。在 AA 中，339 名（12%）患有儿童哮喘。在 AA 或结合 NHW 和 AA 受试者的荟萃分析中，没有 SNP 达到全基因组显着性；然而，已经确定了潜在的感兴趣区域。对已建立的哮喘 SNP 进行了检查，其中 7 个来自 NHGRI-EBI 数据库，5 个在最大的儿科哮喘 GWAS 中具有全基因组意义。在当前的儿童哮喘 GWAS 中发现了与 GSDMB 附近的 IL1RL1、IL13、LINC01149 和 C11orf30-LRRC32 区域中已知哮喘位点的关联（Bonferroni 对所有比较进行了调整 p<0.05）。儿童哮喘患者患慢性阻塞性肺病的风险增加。通过自我报告定义哮喘对于有慢性阻塞性肺病风险的人群是有效的，可以识别具有已知与儿童哮喘相关的临床和遗传特征的受试者。这有可能提高临床对哮喘-慢性阻塞性肺病重叠 (ACO) 的理解，并加强对 ACO 特异性治疗方案的未来研究。 ClinicalTrials.gov，NCT00608764（自 2008 年 1 月 28 日起生效）。本文的在线版本 (10.1186/s12931-018-0890-0) 包含补充材料，可供授权用户使用。
Childhood asthma is strongly influenced by genetics and is a risk factor for reduced lung function and chronic obstructive pulmonary disease (COPD) in adults. This study investigates self-reported childhood asthma in adult smokers from the COPDGene Study. We hypothesize that childhood asthma is associated with decreased lung function, increased risk for COPD, and that a genome-wide association study (GWAS) will show association with established asthma variants. We evaluated current and former smokers ages 45–80 of non-Hispanic white (NHW) or African American (AA) race. Childhood asthma was defined by self-report of asthma, diagnosed by a medical professional, with onset at < 16 years or during childhood. Subjects with a history of childhood asthma were compared to those who never had asthma based on lung function, development of COPD, and genetic variation. GWAS was performed in NHW and AA populations, and combined in meta-analysis. Two sets of established asthma SNPs from published literature were examined for association with childhood asthma. Among 10,199 adult smokers, 730 (7%) reported childhood asthma and 7493 (73%) reported no history of asthma. Childhood asthmatics had reduced lung function and increased risk for COPD (OR 3.42, 95% CI 2.81–4.18). Genotype data was assessed for 8031 subjects. Among NHWs, 391(7%) had childhood asthma, and GWAS identified one genome-wide significant association in KIAA1958 (rs59289606, p = 4.82 × 10− 8). Among AAs, 339 (12%) had childhood asthma. No SNPs reached genome-wide significance in the AAs or in the meta-analysis combining NHW and AA subjects; however, potential regions of interest were identified. Established asthma SNPs were examined, seven from the NHGRI-EBI database and five with genome-wide significance in the largest pediatric asthma GWAS. Associations were found in the current childhood asthma GWAS with known asthma loci in IL1RL1, IL13, LINC01149, near GSDMB, and in the C11orf30-LRRC32 region (Bonferroni adjusted p < 0.05 for all comparisons). Childhood asthmatics are at increased risk for COPD. Defining asthma by self-report is valid in populations at risk for COPD, identifying subjects with clinical and genetic characteristics known to associate with childhood asthma. This has potential to improve clinical understanding of asthma-COPD overlap (ACO) and enhance future research into ACO-specific treatment regimens. ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008). The online version of this article (10.1186/s12931-018-0890-0) contains supplementary material, which is available to authorized users.
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影响因子：
14.2
作者：
Ferreira, Manuel A. R.;Matheson, Melanie C.;Tang, Clara S.;Granell, Raquel;Ang, Wei;Hui, Jennie;Kiefer, Amy K.;Duffy, David L.;Baltic, Svetlana;Danoy, Patrick;Bui, Minh;Price, Loren;Sly, Peter D.;Eriksson, Nicholas;Madden, Pamela A.;Abramson, Michael J.;Holt, Patrick G.;Heath, Andrew C.;Hunter, Michael;Musk, Bill;Robertson, Colin F.;Le Souef, Peter;Montgomery, Grant W.;Henderson, A. John;Tung, Joyce Y.;Dharmage, Shyamali C.;Brown, Matthew A.;James, Alan;Thompson, Philip J.;Pennell, Craig;Martin, Nicholas G.;Evans, David M.;Hinds, David A.;Hopper, John L.
通讯作者：
Hopper, John L.
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
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影响因子：
168.9
作者：
Ferreira, Manuel A. R.;Matheson, Melanie C.;Duffy, David L.;Marks, Guy B.;Hui, Jennie;Le Souef, Peter;Danoy, Patrick;Baltic, Svetlana;Nyholt, Dale R.;Jenkins, Mark;Hayden, Catherine;Willemsen, Gonneke;Ang, Wei;Kuokkanen, Mikko;Beilby, John;Cheah, Faang;de Geus, Eco J. C.;Ramasamy, Adaikalavan;Vedantam, Sailaja;Salomaa, Veikko;Madden, Pamela A.;Heath, Andrew C.;Hopper, John L.;Visscher, Peter M.;Musk, Bill;Leeder, Stephen R.;Jarvelin, Marjo-Riitta;Pennell, Craig;Boomsma, Dorret I.;Hirschhorn, Joel N.;Walters, Haydn;Martin, Nicholas G.;James, Alan;Jones, Graham;Abramson, Michael J.;Robertson, Colin F.;Dharmage, Shyamali C.;Brown, Matthew A.;Montgomery, Grant W.;Thompson, Philip J.
通讯作者：
Thompson, Philip J.
影响因子：
30.8
作者：
Demenais F;Margaritte-Jeannin P;Barnes KC;Cookson WOC;Altmüller J;Ang W;Barr RG;Beaty TH;Becker AB;Beilby J;Bisgaard H;Bjornsdottir US;Bleecker E;Bønnelykke K;Boomsma DI;Bouzigon E;Brightling CE;Brossard M;Brusselle GG;Burchard E;Burkart KM;Bush A;Chan-Yeung M;Chung KF;Couto Alves A;Curtin JA;Custovic A;Daley D;de Jongste JC;Del-Rio-Navarro BE;Donohue KM;Duijts L;Eng C;Eriksson JG;Farrall M;Fedorova Y;Feenstra B;Ferreira MA;Australian Asthma Genetics Consortium (AAGC) collaborators;Freidin MB;Gajdos Z;Gauderman J;Gehring U;Geller F;Genuneit J;Gharib SA;Gilliland F;Granell R;Graves PE;Gudbjartsson DF;Haahtela T;Heckbert SR;Heederik D;Heinrich J;Heliövaara M;Henderson J;Himes BE;Hirose H;Hirschhorn JN;Hofman A;Holt P;Hottenga J;Hudson TJ;Hui J;Imboden M;Ivanov V;Jaddoe VWV;James A;Janson C;Jarvelin MR;Jarvis D;Jones G;Jonsdottir I;Jousilahti P;Kabesch M;Kähönen M;Kantor DB;Karunas AS;Khusnutdinova E;Koppelman GH;Kozyrskyj AL;Kreiner E;Kubo M;Kumar R;Kumar A;Kuokkanen M;Lahousse L;Laitinen T;Laprise C;Lathrop M;Lau S;Lee YA;Lehtimäki T;Letort S;Levin AM;Li G;Liang L;Loehr LR;London SJ;Loth DW;Manichaikul A;Marenholz I;Martinez FJ;Matheson MC;Mathias RA;Matsumoto K;Mbarek H;McArdle WL;Melbye M;Melén E;Meyers D;Michel S;Mohamdi H;Musk AW;Myers RA;Nieuwenhuis MAE;Noguchi E;O'Connor GT;Ogorodova LM;Palmer CD;Palotie A;Park JE;Pennell CE;Pershagen G;Polonikov A;Postma DS;Probst-Hensch N;Puzyrev VP;Raby BA;Raitakari OT;Ramasamy A;Rich SS;Robertson CF;Romieu I;Salam MT;Salomaa V;Schlünssen V;Scott R;Selivanova PA;Sigsgaard T;Simpson A;Siroux V;Smith LJ;Solodilova M;Standl M;Stefansson K;Strachan DP;Stricker BH;Takahashi A;Thompson PJ;Thorleifsson G;Thorsteinsdottir U;Tiesler CMT;Torgerson DG;Tsunoda T;Uitterlinden AG;van der Valk RJP;Vaysse A;Vedantam S;von Berg A;von Mutius E;Vonk JM;Waage J;Wareham NJ;Weiss ST;White WB;Wickman M;Widén E;Willemsen G;Williams LK;Wouters IM;Yang JJ;Zhao JH;Moffatt MF;Ober C;Nicolae DL
通讯作者：
Nicolae DL
影响因子：
30.8
作者：
通讯作者：
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