Genome-wide association study identifies TNFSF15 associated with childhood asthma.
Genome-wide association study identifies TNFSF15 associated with childhood asthma.
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作者：
Kim KW;Kim DY;Yoon D;Kim KK;Jang H;Schoettler N;Kim EG;Kim MN;Hong JY;Lee JK;Kim S;Ober C;Gee HY;Sohn MH
哮喘全基因组关联研究 (GWAS) 已确定了几个风险等位基因和基因座，但大多数是在欧洲血统的个体中进行的。对亚洲人，尤其是儿童的研究仍然缺乏。我们的目的是通过对患有持续性哮喘的韩国儿童进行首次哮喘 GWAS 来确定易感位点。我们使用 741 名患有持续性哮喘的儿童作为病例、589 名健康儿童和 551 名健康成人作为对照来进行 GWAS。我们使用英国生物银行数据验证了 GWAS 研究结果。然后，我们使用基因型-组织表达数据库来识别候选变体的表达数量性状基因座。最后，我们定量了与哮喘相关的基因的蛋白质。 CYBRD1 和 TNFSF15 基因中 17q12-21 位点的变异和 SNP 与全基因组显着性阈值下的持续性儿童哮喘相关。英国生物银行数据显示，TNFSF15 基因中的四个 SNP 也与英国白人参与者的儿童期哮喘相关。哮喘相关的 rs7856856-C 等位基因（主要 SNP）与全血和动脉中 TNFSF15 表达降低相关。韩国哮喘儿童的血清 TNFSF15 水平低于对照组，而具有哮喘风险 rs7856856-CC 基因型的儿童整体血清 TNFSF15 水平最低，尤其是哮喘儿童。我们对伴有过敏致敏的持续性儿童哮喘的 GWAS 发现了一种新的易感基因 TNFSF15，并在 17q12-21 儿童发病哮喘基因座上复制了关联。这种新的关联可能是通过血清 TNFSF15 表达减少和血管生成抑制作用丧失介导的。我们的全基因组关联研究发现了一种新的易感基因 TNFSF15，它与儿童持续性哮喘有关。哮喘儿童的血清 TNFSF15 水平低于对照组，而具有哮喘风险 rs7856856-CC 基因型的儿童的血清 TNFSF15 水平最低。这种新的关联可能是通过降低 TNFSF15 的表达而失去对血管生成的抑制来介导的。
Genome-wide association studies (GWASs) of asthma have identified several risk alleles and loci, but most have been conducted in individuals with European-ancestry. Studies in Asians, especially children, are still lacking. We aimed to identify susceptibility loci by performing the first GWAS of asthma in Korean children with persistent asthma. We used a discovery set of 741 children with persistent asthma as cases and 589 healthy children and 551 healthy adults as controls to perform a GWAS. We validated our GWAS findings using UK Biobank data. We then used the Genotype-Tissue Expression database to identify expression quantitative trait loci of candidate variants. Finally, we quantified proteins of genes associated with asthma. Variants at the 17q12–21 locus and SNPs in CYBRD1 and TNFSF15 genes were associated with persistent childhood asthma at genome-wide thresholds of significance. Four SNPs in the TNFSF15 gene were also associated with childhood-onset asthma in British white participants in the UK Biobank data. The asthma-associated rs7856856-C allele, the lead SNP, was associated with decreased TNFSF15 expression in whole blood and in arteries. Korean children with asthma had lower serum TNFSF15 levels than controls, and those with the asthma risk rs7856856-CC genotype exhibited the lowest serum TNFSF15 levels overall, especially asthmatic children. Our GWAS of persistent childhood asthma with allergic sensitization identified a new susceptibility gene, TNFSF15, and replicated associations at the 17q12–21 childhood-onset asthma locus. This novel association may be mediated by reduced expression of serum TNFSF15 and loss of suppression of angiogenesis. Our genome-wide association studies identify a new susceptibility gene, TNFSF15 for persistent asthma in children. Children with asthma have lower serum TNFSF15 levels than controls, and those with the asthma risk rs7856856-CC genotype exhibit the lowest serum TNFSF15 levels. This novel association may be mediated by loss of suppression of angiogenesis via lower expression of TNFSF15.
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影响因子：
3.7
作者：
Baye TM;Butsch Kovacic M;Biagini Myers JM;Martin LJ;Lindsey M;Patterson TL;He H;Ericksen MB;Gupta J;Tsoras AM;Lindsley A;Rothenberg ME;Wills-Karp M;Eissa NT;Borish L;Khurana Hershey GK
通讯作者：
Khurana Hershey GK
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
4.5
作者：
Noguchi E;Sakamoto H;Hirota T;Ochiai K;Imoto Y;Sakashita M;Kurosaka F;Akasawa A;Yoshihara S;Kanno N;Yamada Y;Shimojo N;Kohno Y;Suzuki Y;Kang MJ;Kwon JW;Hong SJ;Inoue K;Goto Y;Yamashita F;Asada T;Hirose H;Saito I;Fujieda S;Hizawa N;Sakamoto T;Masuko H;Nakamura Y;Nomura I;Tamari M;Arinami T;Yoshida T;Saito H;Matsumoto K
通讯作者：
Matsumoto K
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：
Ellinghaus D;Jostins L;Spain SL;Cortes A;Bethune J;Han B;Park YR;Raychaudhuri S;Pouget JG;Hübenthal M;Folseraas T;Wang Y;Esko T;Metspalu A;Westra HJ;Franke L;Pers TH;Weersma RK;Collij V;D'Amato M;Halfvarson J;Jensen AB;Lieb W;Degenhardt F;Forstner AJ;Hofmann A;International IBD Genetics Consortium (IIBDGC);International Genetics of Ankylosing Spondylitis Consortium (IGAS);International PSC Study Group (IPSCSG);Genetic Analysis of Psoriasis Consortium (GAPC);Psoriasis Association Genetics Extension (PAGE);Schreiber S;Mrowietz U;Juran BD;Lazaridis KN;Brunak S;Dale AM;Trembath RC;Weidinger S;Weichenthal M;Ellinghaus E;Elder JT;Barker JN;Andreassen OA;McGovern DP;Karlsen TH;Barrett JC;Parkes M;Brown MA;Franke A
通讯作者：
Franke A