Genome-wide association study of preserved ratio impaired spirometry (PRISm).
Genome-wide association study of preserved ratio impaired spirometry (PRISm).
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DOI：
10.1183/13993003.00337-2023
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发表时间：
2024-01
影响因子：
24.3
通讯作者：
Dodd, James W.
中科院分区：
文献类型：
--
作者：
Higbee, Daniel H.;Lirio, Alvin;Hamilton, Fergus;Granell, Raquel;Wyss, Annah B.;London, Stephanie J.;Bartz, Traci M.;Gharib, Sina A.;Cho, Michael H.;Wan, Emily;Silverman, Edwin;Crapo, James D.;Lominchar, Jesus V. T.;Hansen, Torben;Grarup, Niels;Dantoft, Thomas;Karhus, Line;Linneberg, Allan;O'Connor, George T.;Dupuis, Josee;Xu, Hanfie;De Vries, Maaike M.;Hu, Xiaowei;Rich, Stephen S.;Barr, R. Graham;Manichaikul, Ani;Wijnant, Sara R. A.;Brusselle, Guy G.;Lahousse, Lies;Li, Xuan;Cordero, Ana I. Hernandez;Obeidat, Ma'en;Sin, Don D.;Harris, Sarah E.;Redmond, Paul;Taylor, Adele M.;Cox, Simon R.;Williams, Alexander T.;Shrine, Nick;John, Catherine;Guyatt, Anna L.;Hall, Ian P.;Smith, George Davey;Tobin, Martin D.;Dodd, James W.
保留比肺功能受损（PRISm）定义为1秒内用力呼气量(FEV1) <预测值的80%，FEV1/用力肺活量≥0.70。PRISm与呼吸道症状和合并症有关。我们的目标是发现PRISm的新遗传信号，并看看它们是否为PRISm的发病机制和相关合并症提供了见解。我们在UK Biobank参与者中进行了PRISm的全基因组关联研究（GWAS）（第一阶段），并在13个队列中选择了具有全基因组意义的单核苷酸多态性（snp）进行复制（第二阶段）。对第一阶段和第二阶段进行综合荟萃分析以确定顶级snp。我们使用跨性状连锁不平衡评分回归来估计PRISm与肺和肺外性状之间的全基因组遗传相关性。对顶级snp进行全现象关联研究。22个信号在联合meta分析中达到显著性，包括4个肺功能的新信号。PRISm与肺活量计COPD之间存在很强的全基因组遗传相关性（rg=0.62, p<0.001），与2型糖尿病之间存在遗传相关性（rg=0.12, p=0.007）。全现象关联研究表明，22个信号中有18个与糖尿病特征有关，7个与血压特征有关。这是第一个成功识别与PRISm相关的snp的GWAS。其中四个信号rs7652391（最近基因MECOM）、rs9431040 （HLX）、rs62018863 （TMEM114）和rs185937162 （HLA-B）与肺功能的关联此前未被描述，这表明在GWAS中使用不同肺功能表型的效用。与PRISm相关的遗传因素与其他肺部疾病和肺外合并症的风险密切相关。这是第一个报道PRISm全基因组显著snp的GWAS，其中四个是肺功能的新snp。与PRISm相关的遗传因素与其他肺部疾病和肺外合并症的风险密切相关。https://bit.ly/3Qo0jUn
Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV1) <80% predicted and FEV1/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities. We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed. 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (rg) between PRISm and spirometric COPD (rg=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (rg=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits. This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 (HLX), rs62018863 (TMEM114) and rs185937162 (HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity. This is the first GWAS to report genome-wide significant SNPs for PRISm, four of which are novel for lung function. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity. https://bit.ly/3Qo0jUn
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影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Shrine, Nick;Izquierdo, Abril G.;Chen, Jing;Packer, Richard;Hall, Robert J.;Guyatt, Anna L.;Batini, Chiara;Thompson, Rebecca J.;Pavuluri, Chandan;Malik, Vidhi;Hobbs, Brian D.;Moll, Matthew;Kim, Wonji;Tal-Singer, Ruth;Bakke, Per;Fawcett, Katherine A.;John, Catherine;Coley, Kayesha;Piga, Noemi Nicole;Pozarickij, Alfred;Lin, Kuang;Millwood, Iona Y.;Chen, Zhengming;Li, Liming;Wijnant, Sara R. A.;Lahousse, Lies;Brusselle, Guy;Uitterlinden, Andre G.;Manichaikul, Ani;Oelsner, Elizabeth C.;Rich, Stephen S.;Barr, R. Graham;Kerr, Shona M.;Vitart, Veronique;Brown, Michael R.;Wielscher, Matthias;Imboden, Medea;Jeong, Ayoung;Bartz, Traci M.;Gharib, Sina A.;Flexeder, Claudia;Karrasch, Stefan;Gieger, Christian;Peters, Annette;Stubbe, Beate;Hu, Xiaowei;Ortega, Victor E.;Meyers, Deborah A.;Bleecker, Eugene R.;Gabriel, Stacey B.;Gupta, Namrata;Smith, Albert Vernon;Luan, Jian'an;Zhao, Jing-Hua;Hansen, Ailin F.;Langhammer, Arnulf;Willer, Cristen;Bhatta, Laxmi;Porteous, David;Smith, Blair H.;Campbell, Archie;Sofer, Tamar;Lee, Jiwon;Daviglus, Martha L.;Yu, Bing;Lim, Elise;Xu, Hanfei;O'Connor, George T.;Thareja, Gaurav;Albagha, Omar M. E.;Ismail, Said I.;Al-Muftah, Wadha;Badji, Radja;Mbarek, Hamdi;Darwish, Dima;Fadl, Tasnim;Yasin, Heba;Ennaifar, Maryem;Abdellatif, Rania;Alkuwari, Fatima;Alvi, Muhammad;Al-Sarraj, Yasser;Saad, Chadi;Althani, Asmaa;Fethnou, Eleni;Qafoud, Fatima;Alkhayat, Eiman;Afifi, Nahla;Tomei, Sara;Liu, Wei;Lorenz, Stephan;Syed, Najeeb;Almabrazi, Hakeem;Vempalli, Fazulur Rehaman;Temanni, Ramzi;Abu Saqri, Tariq;Khatib, Mohammedhusen;Hamza, Mehshad;Abu Zaid, Tariq;El Khouly, Ahmed;Pathare, Tushar;Poolat, Shafeeq;Al-Ali, Rashid;Al-Khodor, Souhaila;Alshafai, Mashael;Badii, Ramin;Chouchane, Lotfi;Estivill, Xavier;Fakhro, Khalid;Mokrab, Younes;Puthen, Jithesh, V;Tatari, Zohreh;Suhre, Karsten;Granell, Raquel;Faquih, Tariq O.;Hiemstra, Pieter S.;Slats, Annelies M.;Mullin, Benjamin H.;Hui, Jennie;James, Alan;Beilby, John;Patasova, Karina;Hysi, Pirro;Koskela, Jukka T.;Wyss, Annah B.;Jin, Jianping;Sikdar, Sinjini;Lee, Mikyeong;May-Wilson, Sebastian;Pirastu, Nicola;Kentistou, Katherine A.;Joshi, Peter K.;Timmers, Paul R. H. J.;Williams, Alexander T.;Free, Robert C.;Wang, Xueyang;Morrison, John L.;Gilliland, Frank D.;Chen, Zhanghua;Wang, Carol A.;Foong, Rachel E.;Harris, Sarah E.;Taylor, Adele;Redmond, Paul;Cook, James P.;Mahajan, Anubha;Lind, Lars;Palviainen, Teemu;Lehtimaki, Terho;Raitakari, Olli T.;Kaprio, Jaakko;Rantanen, Taina;Pietilainen, Kirsi H.;Cox, Simon R.;Pennell, Craig E.;Hall, Graham L.;Gauderman, W. James;Brightling, Chris;Wilson, James F.;Vasankari, Tuula;Laitinen, Tarja;Salomaa, Veikko;Mook-Kanamori, Dennis O.;Timpson, Nicholas J.;Zeggini, Eleftheria;Dupuis, Josee;Hayward, Caroline;Brumpton, Ben;Langenberg, Claudia;Weiss, Stefan;Homuth, Georg;Schmidt, Carsten Oliver;Probst-Hensch, Nicole;Jarvelin, Marjo-Riitta;Morrison, Alanna C.;Polasek, Ozren;Rudan, Igor;Lee, Joo-Hyeon;Sayers, Ian;Rawlins, Emma L.;Dudbridge, Frank;Silverman, Edwin K.;Strachan, David P.;Walters, Robin G.;Morris, Andrew P.;London, Stephanie J.;Cho, Michael H.;Wain, Louise, V;Hall, Ian P.;Tobin, Martin
通讯作者：
Tobin, Martin
影响因子：
10
作者：
Guerra S;Sherrill DL;Venker C;Ceccato CM;Halonen M;Martinez FD
通讯作者：
Martinez FD
影响因子：
30.8
作者：
Loh, Po-Ru;Tucker, George;Bulik-Sullivan, Brendan K.;Vilhjalmsson, Bjarni J.;Finucane, Hilary K.;Salem, Rany M.;Chasman, Daniel I.;Ridker, Paul M.;Neale, Benjamin M.;Berger, Bonnie;Patterson, Nick;Price, Alkes L.
通讯作者：
Price, Alkes L.
DOI：
10.1164/rccm.201804-0663oc
发表时间：
2018-12-01
影响因子：
24.7
作者：
Wan, Emily S.;Fortis, Spyridon;Silverman, Edwin K.
通讯作者：
Silverman, Edwin K.