Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.
Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.
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多血统全基因组关联分析提高了对影响肺功能和慢性阻塞性肺疾病风险的基因及通路的解析度。
DOI：
10.1038/s41588-023-01314-0
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发表时间：
2023-03
期刊：
影响因子：
30.8
通讯作者：
Tobin, Martin
中科院分区：
文献类型：
--
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
肺功能损害是慢性阻塞性肺疾病（COPD）的基础，可预测死亡率。在迄今为止最大的肺功能多祖先全基因组关联荟萃分析中，包括588，452名参与者，我们从系统性变体-基因作图框架中确定了1，020个独立关联信号，涉及559个基因，并得到≥2个标准的支持。这些基因在29条通路中富集。个体变异在祖先、年龄和吸烟组之间显示出异质性，并且作为遗传风险评分，总体上显示出与各祖先组的COPD的强相关性。我们对选定的相关变异以及性状和途径特异性遗传风险评分进行了全表型关联研究，以推断干预肺功能相关途径的可能后果。我们强调了新的推定的因果变异，基因，蛋白质和途径，包括现有药物的目标。这些发现使我们更接近了解肺功能和COPD的潜在机制，并应告知功能基因组学实验和未来的COPD治疗。多祖先全基因组关联分析和系统性变异-基因定位策略提示影响肺功能和慢性阻塞性肺疾病风险的新基因和途径。
Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 588,452 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies. Multi-ancestry genome-wide association analyses and systematic variant-to-gene mapping strategies implicate new genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.
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影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
全基因组关联荟萃分析产生了20个与胆结石疾病相关的基因座。
影响因子：
16.6
作者：
Ferkingstad E;Oddsson A;Gretarsdottir S;Benonisdottir S;Thorleifsson G;Deaton AM;Jonsson S;Stefansson OA;Norddahl GL;Zink F;Arnadottir GA;Gunnarsson B;Halldorsson GH;Helgadottir A;Jensson BO;Kristjansson RP;Sveinbjornsson G;Sverrisson DA;Masson G;Olafsson I;Eyjolfsson GI;Sigurdardottir O;Holm H;Jonsdottir I;Olafsson S;Steingrimsdottir T;Rafnar T;Bjornsson ES;Thorsteinsdottir U;Gudbjartsson DF;Sulem P;Stefansson K
通讯作者：
Stefansson K
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：
16.6
作者：
Soler Artigas M;Wain LV;Miller S;Kheirallah AK;Huffman JE;Ntalla I;Shrine N;Obeidat M;Trochet H;McArdle WL;Alves AC;Hui J;Zhao JH;Joshi PK;Teumer A;Albrecht E;Imboden M;Rawal R;Lopez LM;Marten J;Enroth S;Surakka I;Polasek O;Lyytikäinen LP;Granell R;Hysi PG;Flexeder C;Mahajan A;Beilby J;Bossé Y;Brandsma CA;Campbell H;Gieger C;Gläser S;González JR;Grallert H;Hammond CJ;Harris SE;Hartikainen AL;Heliövaara M;Henderson J;Hocking L;Horikoshi M;Hutri-Kähönen N;Ingelsson E;Johansson Å;Kemp JP;Kolcic I;Kumar A;Lind L;Melén E;Musk AW;Navarro P;Nickle DC;Padmanabhan S;Raitakari OT;Ried JS;Ripatti S;Schulz H;Scott RA;Sin DD;Starr JM;UK BiLEVE;Viñuela A;Völzke H;Wild SH;Wright AF;Zemunik T;Jarvis DL;Spector TD;Evans DM;Lehtimäki T;Vitart V;Kähönen M;Gyllensten U;Rudan I;Deary IJ;Karrasch S;Probst-Hensch NM;Heinrich J;Stubbe B;Wilson JF;Wareham NJ;James AL;Morris AP;Jarvelin MR;Hayward C;Sayers I;Strachan DP;Hall IP;Tobin MD
通讯作者：
Tobin MD
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL