慢性阻塞性肺疾病全基因组关联研究进展

doi:10.16288/j.yczz.19-381

遗传 ›› 2020, Vol. 42 ›› Issue (9): 832-846.doi: 10.16288/j.yczz.19-381

慢性阻塞性肺疾病全基因组关联研究进展

钱国清^1,^2,³

^1. 宁波大学附属宁波市第一医院内科,宁波 315010
^2. 浙江大学宁波医院呼吸科,宁波 315010
^3. 英国诺丁汉大学医学院,诺丁汉 NG7 2RD

收稿日期:2020-02-25 修回日期:2020-05-29 出版日期:2020-09-20 发布日期:2020-06-19
作者简介:钱国清,博士,副主任医师,研究方向：呼吸病学。E-mail: guoqing.qian@foxmail.com
基金资助:
宁波市自然科学基金项目资助编号(Q17H010001);宁波市自然科学基金项目资助编号(2017A610246)

Advances in genome-wide association study of chronic obstructive pulmonary disease

Guoqing Qian^1,^2,³

^1. Department of General Internal Medicine, Ningbo First Hospital, Ningbo University, Ningbo 315010, China
^2. Department of Respiratory Medicine, Ningbo Hospital of Zhejiang University, Ningbo 315010, China
^3. Shool of Medicine, University of Nottingham, Nottingham UK NG7 2RD, UK

Received:2020-02-25 Revised:2020-05-29 Online:2020-09-20 Published:2020-06-19
Supported by:
Supported by the Natural Science Foundation of Zhejiang Province No(Q17H010001);the Natural Science Foundation of Ningbo City No(2017A610246)

摘要/Abstract

摘要：

慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)是一种以不完全可逆的气流受限为主要特征的慢性气道炎症,是一种由遗传因素和环境因素共同作用的复杂疾病,也是世界主要致死疾病之一。近年来,随着全基因组关联研究(genome-wide association study, GWAS)的不断深入,研究者们发现了大量与肺功能或COPD相关的遗传变异或基因位点、药物靶点等。本文综述了2007年以来世界范围内针对肺功能或COPD的GWAS方面的研究工作及其进展综述,分析了可能存在的药物靶点,并探讨了COPD在全基因组关联研究中面临的挑战和困难,为深入研究COPD发病机制提供新思路。

关键词: 慢性阻塞性肺疾病, 肺功能, 全基因组关联研究, 遗传变异, 基因座, 易感基因, 致病基因

Abstract:

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and chronic airway inflammation, caused by a combination of environmental and genetic factors. It is the third leading cause of death worldwide. In recent years, researchers have applied the genome-wide association study (GWAS) and identified a large number of genetic variants associated with lung functions and potential drug targets for treating COPD. In this review, we summarize the results of GWAS studies and perform a review of the literature since 2007 to highlight the progress of GWAS on COPD. We discuss the challenges, the underlying mechanisms, and the possible drug targets, thereby providing insights on the pathogenesis and potential treatment strategies for COPD.

Key words: chronic obstructive pulmonary disease, lung function, genome-wide association study, genetic variant, locus, susceptibility gene, causal gene

钱国清. 慢性阻塞性肺疾病全基因组关联研究进展[J]. 遗传, 2020, 42(9): 832-846.

Guoqing Qian. Advances in genome-wide association study of chronic obstructive pulmonary disease[J]. Hereditas(Beijing), 2020, 42(9): 832-846.

图/表 6

图1

图2

表1

表2

表3

表4

参考文献 62

[1]	GOLD. The Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (Updated 2019). 2019 .
[2]	Wang C, Xu JY, Yang L, Xu YJ, Zhang XY, Bai CX, Kang J, Ran PX, Shen HH, Wen FQ, Huang KW, Yao WZ, Sun TY, Shan GL, Yang T, Lin YX, Wu SN, Zhu JG, Wang RY, Shi ZH, Zhao JP, Ye XW, Song YL, Wang QY, Zhou YM, Ding LR, Yang T, Chen YH, Guo YF, Xiao F, Lu Y, Peng XX, Zhang B, Xiao D, Chen CS, Wang ZM, Zhang H, Bu XN, Zhang XL, An L, Zhang S, Cao ZX, Zhan QY, Yang YH, Cao B, Dai HP, Liang LR, He J . Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet, 2018,391(10131):1706-1717. doi: 10.1016/S0140-6736(18)30841-9 pmid: 29650248
[3]	Collaborators GCRD. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med, 2017,5(9):691-706. doi: 10.1016/S2213-2600(17)30293-X pmid: 28822787
[4]	Kheirallah AK, Miller S, Hall IP, Sayers I . Translating lung function genome-wide association study (GWAS) findings: new insights for lung biology. Adv Genet, 2016,93:57-145. doi: 10.1016/bs.adgen.2015.12.002 pmid: 26915270
[5]	Wain LV, Shrine N, Miller S, Jackson VE, Ntalla I, Artigas MS, Billington CK, Kheirallah AK, Allen R, Cook JP, Probert K, Obeidat Me, Bossé Y, Hao K, Postma DS, Paré PD, Ramasamy A, Mägi R, Mihailov E, Reinmaa E, Melén E, O'Connell J, Frangou E, Delaneau O, Freeman C, Petkova D, McCarthy M, Sayers I, Deloukas P, Hubbard R, Pavord I, Hansell AL, Thomson NC, Zeggini E, Morris AP, Marchini J, Strachan DP, Tobin MD, Hall IP. Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank. Lancet Respir Med, 2015,3(10):769-781. doi: 10.1016/S2213-2600(15)00283-0 pmid: 26423011
[6]	Salvi SS, Barnes PJ . Chronic obstructive pulmonary disease in non-smokers. Lancet, 2009,374(9691):733-743. doi: 10.1016/S0140-6736(09)61303-9 pmid: 19716966
[7]	Liang WQ, Hou Y, Zhao CY . Schizophrenia-associated single nucleotide polymorphisms affecting microRNA function. Hereditas(Beijing), 2019,41(8):677-685.
	梁文权, 侯豫, 赵存友 . 精神分裂症相关单核苷酸多态性调控microRNA功能研究进展. 遗传, 2019,41(8):677-685.
[8]	Wang YY, Wang ZX, Hu YD, Wang L, Li N, Zhang B, Han W, Jiang JM . Current status of pathway analysis in genome-wide association study. Hereditas(Beijing), 2017,39(8):707-716.
	王钰嫣, 王子兴, 胡耀达, 王蕾, 李宁, 张彪, 韩伟, 姜晶梅 . 全基因组关联研究通路分析方法现状. 遗传, 2017,39(8):707-716.
[9]	Obeidat M, Hall IP . Genetics of complex respiratory diseases: implications for pathophysiology and pharmacology studies. Bri J Pharmacol, 2011,163(1):96-105.
[10]	Hobbs BD, de Jong K, Lamontagne M, Bosse Y, Shrine N, Artigas MS, Wain LV, Hall IP, Jackson VE, Wyss AB, London SJ, North KE, Franceschini N, Strachan DP, Beaty TH, Hokanson JE, Crapo JD, Castaldi PJ, Chase RP, Bartz TM, Heckbert SR, Psaty BM, Gharib SA, Zanen P, Lammers JW, Oudkerk M, Groen HJ, Locantore N, Tal-Singer R, Rennard SI, Vestbo J, Timens W, Pare PD, Latourelle JC, Dupuis J, O'Connor GT, Wilk JB, Kim WJ, Lee MK, Oh YM, Vonk JM, de Koning HJ, Leng S, Belinsky SA, Tesfaigzi Y, Manichaikul A, Wang XQ, Rich SS, Barr RG, Sparrow D, Litonjua AA, Bakke P, Gulsvik A, Lahousse L, Brusselle GG, Stricker BH, Uitterlinden AG, Ampleford EJ, Bleecker ER, Woodruff PG, Meyers DA, Qiao D, Lomas DA, Yim JJ, Kim DK, Hawrylkiewicz I, Sliwinski P, Hardin M, Fingerlin TE, Schwartz DA, Postma DS, MacNee W, Tobin MD, Silverman EK, Boezen HM, Cho MH . Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis. Nat Genet, 2017,49(3):426-432. doi: 10.1038/ng.3752 pmid: 28166215
[11]	Hubert HB, Fabsitz RR, Feinleib M, Gwinn C . Genetic and environmental influences on pulmonary function in adult twins. Am Rev Respir Dis, 1982,125(4):409-415. doi: 10.1164/arrd.1982.125.4.409 pmid: 7200340
[12]	Hall R, Hall IP, Sayers I . Genetic risk factors for the development of pulmonary disease identified by genome- wide association. Respirology, 2019,24(3):204-214. doi: 10.1111/resp.13436 pmid: 30421854
[13]	Wain LV, Shrine N, Artigas MS, Erzurumluoglu AM, Noyvert B, Bossini-Castillo L, Obeidat M, Henry AP, Portelli MA, Hall RJ, Billington CK, Rimington TL, Fenech AG, John C, Blake T, Jackson VE, Allen RJ, Prins BP, Campbell A, Porteous DJ, Jarvelin MR, Wielscher M, James AL, Hui J, Wareham NJ, Zhao JH, Wilson JF, Joshi PK, Stubbe B, Rawal R, Schulz H, Imboden M, Probst-Hensch NM, Karrasch S, Gieger C, Deary IJ, Harris SE, Marten J, Rudan I, Enroth S, Gyllensten U, Kerr SM, Polasek O, Kahonen M, Surakka I, Vitart V, Hayward C, Lehtimaki T, Raitakari OT, Evans DM, Henderson AJ, Pennell CE, Wang CA, Sly PD, Wan ES, Busch R, Hobbs BD, Litonjua AA, Sparrow DW, Gulsvik A, Bakke PS, Crapo JD, Beaty TH, Hansel NN, Mathias RA, Ruczinski I, Barnes KC, Bosse Y, Joubert P, van den Berge M, Brandsma CA, Pare PD, Sin DD, Nickle DC, Hao K, Gottesman O, Dewey FE, Bruse SE, Carey DJ, Kirchner HL, Jonsson S, Thorleifsson G, Jonsdottir I, Gislason T, Stefansson K, Schurmann C, Nadkarni G, Bottinger EP, Loos RJ, Walters RG, Chen Z, Millwood IY, Vaucher J, Kurmi OP, Li L, Hansell AL, Brightling C, Zeggini E, Cho MH, Silverman EK, Sayers I, Trynka G, Morris AP, Strachan DP, Hall IP, Tobin MD. Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets. Nat Genet, 2017,49(3):416-425. doi: 10.1038/ng.3787 pmid: 28166213
[14]	Wilk JB, Walter RE, Laramie JM, Gottlieb DJ, O'Connor GT,. Framingham Heart Study genome-wide association: results for pulmonary function measures. BMC Med Genet, 2007,8(1):S8. doi: 10.1186/1471-2350-8-S1-S8
[15]	Wilk JB, Chen TH, Gottlieb DJ, Walter RE, Nagle MW, Brandler BJ, Myers RH, Borecki IB, Silverman EK, Weiss ST, O'Connor GT. A genome-wide association study of pulmonary function measures in the Framingham Heart Study. PLoS Genet, 2009,5(3):e1000429. doi: 10.1371/journal.pgen.1000429 pmid: 19300500
[16]	Hancock DB, Eijgelsheim M, Wilk JB, Gharib SA, Loehr LR, Marciante KD, Franceschini N, van Durme YM, Chen TH, Barr RG, Schabath MB, Couper DJ, Brusselle GG, Psaty BM, van Duijn CM, Rotter JI, Uitterlinden AG, Hofman A, Punjabi NM, Rivadeneira F, Morrison AC, Enright PL, North KE, Heckbert SR, Lumley T, Stricker BHC, O'Connor GT, London SJ. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat Genet, 2010,42(1):45-52. doi: 10.1038/ng.500 pmid: 20010835
[17]	Repapi E, Sayers I, Wain LV, Burton PR, Johnson T, Obeidat M, Zhao JH, Ramasamy A, Zhai G, Vitart V, Huffman JE, Igl W, Albrecht E, Deloukas P, Henderson J, Granell R, McArdle WL, Rudnicka AR, Wellcome Trust Case Control C, Barroso I, Loos RJ, Wareham NJ, Mustelin L, Rantanen T, Surakka I, Imboden M, Wichmann HE, Grkovic I, Jankovic S, Zgaga L, Hartikainen AL, Peltonen L, Gyllensten U, Johansson A, Zaboli G, Campbell H, Wild SH, Wilson JF, Glaser S, Homuth G, Volzke H, Mangino M, Soranzo N, Spector TD, Polasek O, Rudan I, Wright AF, Heliovaara M, Ripatti S, Pouta A, Naluai AT, Olin AC, Toren K, Cooper MN, James AL, Palmer LJ, Hingorani AD, Wannamethee SG, Whincup PH, Smith GD, Ebrahim S, McKeever TM, Pavord ID, MacLeod AK, Morris AD, Porteous DJ, Cooper C, Dennison E, Shaheen S, Karrasch S, Schnabel E, Schulz H, Grallert H, Bouatia-Naji N, Delplanque J, Froguel P, Blakey JD, Team NRS, Britton JR, Morris RW, Holloway JW, Lawlor DA, Hui J, Nyberg F, Jarvelin MR, Jackson C, Kahonen M, Kaprio J, Probst-Hensch NM, Koch B, Hayward C, Evans DM, Elliott P, Strachan DP, Hall IP, Tobin MD. Genome-wide association study identifies five loci associated with lung function. Nat Genet, 2010,42(1):36-44. doi: 10.1038/ng.501 pmid: 20010834
[18]	Hancock DB, Soler Artigas M, Gharib SA, Henry A, Manichaikul A, Ramasamy A, Loth DW, Imboden M, Koch B, McArdle WL, Smith AV, Smolonska J, Sood A, Tang W, Wilk JB, Zhai G, Zhao JH, Aschard H, Burkart KM, Curjuric I, Eijgelsheim M, Elliott P, Gu XJ, Harris TB, Janson C, Homuth G, Hysi PG, Liu JZ, Loehr LR, Lohman K, Loos RJ, Manning AK, Marciante KD, Obeidat M, Postma DS, Aldrich MC, Brusselle GG, Chen TH, Eiriksdottir G, Franceschini N, Heinrich J, Rotter JI, Wijmenga C, Williams OD, Bentley AR, Hofman A, Laurie CC, Lumley T, Morrison AC, Joubert BR, Rivadeneira F, Couper DJ, Kritchevsky SB, Liu YM, Wjst M, Wain LV, Vonk JM, Uitterlinden AG, Rochat T, Rich SS, Psaty BM, O'Connor GT, North KE, Mirel DB, Meibohm B, Launer LJ, Khaw KT, Hartikainen AL, Hammond CJ, Glaser S, Marchini J, Kraft P, Wareham NJ, Volzke H, Stricker BH, Spector TD, Probst-Hensch NM, Jarvis D, Jarvelin MR, Heckbert SR, Gudnason V, Boezen HM, Barr RG, Cassano PA, Strachan DP, Fornage M, Hall IP, Dupuis J, Tobin MD, London SJ. Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. PLoS Genet, 2012,8(12):e1003098. doi: 10.1371/journal.pgen.1003098 pmid: 23284291
[19]	Loth DW, Soler Artigas M, Gharib SA, Wain LV, Franceschini N, Koch B, Pottinger TD, Smith AV, Duan Q, Oldmeadow C, Lee MK, Strachan DP, James AL, Huffman JE, Vitart V, Ramasamy A, Wareham NJ, Kaprio J, Wang XQ, Trochet H, Kahonen M, Flexeder C, Albrecht E, Lopez LM, de Jong K, Thyagarajan B, Alves AC, Enroth S, Omenaas E, Joshi PK, Fall T, Vinuela A, Launer LJ, Loehr LR, Fornage M, Li G, Wilk JB, Tang WB, Manichaikul A, Lahousse L, Harris TB, North KE, Rudnicka AR, Hui J, Gu X, Lumley T, Wright AF, Hastie ND, Campbell S, Kumar R, Pin I, Scott RA, Pietilainen KH, Surakka I, Liu YM, Holliday EG, Schulz H, Heinrich J, Davies G, Vonk JM, Wojczynski M, Pouta A, Johansson A, Wild SH, Ingelsson E, Rivadeneira F, Volzke H, Hysi PG, Eiriksdottir G, Morrison AC, Rotter JI, Gao W, Postma DS, White WB, Rich SS, Hofman A, Aspelund T, Couper D, Smith LJ, Psaty BM, Lohman K, Burchard EG, Uitterlinden AG, Garcia M, Joubert BR, McArdle WL, Musk AB, Hansel N, Heckbert SR, Zgaga L, van Meurs JB, Navarro P, Rudan I, Oh YM, Redline S, Jarvis DL, Zhao JH, Rantanen T, O'Connor GT, Ripatti S, Scott RJ, Karrasch S, Grallert H, Gaddis NC, Starr JM, Wijmenga C, Minster RL, Lederer DJ, Pekkanen J, Gyllensten U, Campbell H, Morris AP, Gläser S, Hammond CJ, Burkart KM, Beilby J, Kritchevsky SB, Gudnason V, Hancock DB, Williams OD, Polasek O, Zemunik T, Kolcic I, Petrini MF, Wjst M, Kim WJ, Porteous DJ, Scotland G, Smith BH, Viljanen A, Heliövaara M, Attia JR, Sayers I, Hampel R, Gieger C, Deary IJ, Boezen HM, Newman A, Jarvelin MR, Wilson JF, Lind L, Stricker BH, Teumer A, Spector TD, Melen E, Peters MJ, Lange LA, Barr RG, Bracke KR, Verhamme FM, Sung J, Hiemstra PS, Cassano PA, Sood A, Hayward C, Dupuis J, Hall IP, Brusselle GG, Tobin MD, London SJ. Genome-wide association analysis identifies six new loci associated with forced vital capacity. Nat Genet, 2014,46(7):669-677. doi: 10.1038/ng.3011 pmid: 24929828
[20]	Shrine N, Guyatt AL, Erzurumluoglu AM, Jackson VE, Hobbs BD, Melbourne CA, Batini C, Fawcett KA, Song K, Sakornsakolpat P, Li XN, Boxall R, Reeve NF, Obeidat M, Zhao JH, Wielscher M, Weiss S, Kentistou KA, Cook JP, Sun BB, Zhou J, Hui J, Karrasch S, Imboden M, Harris SE, Marten J, Enroth S, Kerr SM, Surakka I, Vitart V, Lehtimäki T, Allen RJ, Bakke PS, Beaty TH, Bleecker ER, Bossé Y, Brandsma CA, Chen ZM, Crapo JD, Danesh J, DeMeo DL, Dudbridge F, Ewert R, Gieger C, Gulsvik A, Hansell AL, Hao K, Hoffman JD, Hokanson JE, Homuth G, Joshi PK, Joubert P, Langenberg C, Li X, Li LM, Lin K, Lind L, Locantore N, Luan JA, Mahajan A, Maranville JC, Murray A, Nickle DC, Packer R, Parker MM, Paynton ML, Porteous DJ, Prokopenko D, Qiao DD, Rawal R, Runz H, Sayers I, Sin DD, Smith BH, Artigas MS, Sparrow D, Tal-Singer R, Timmers PRHJ, Van den Berge M, Whittaker JC, Woodruff PG, Yerges-Armstrong LM, Troyanskaya OG, Raitakari OT, Kähönen M, Polašek O, Gyllensten U, Rudan I, Deary IJ, Probst-Hensch NM, Schulz H, James AL, Wilson JF, Stubbe B, Zeggini E, Jarvelin MR, Wareham N, Silverman EK, Hayward C, Morris AP, Butterworth AS, Scott RA, Walters RG, Meyers DA, Cho MH, Strachan DP, Hall IP, Tobin MD, Wain LV. New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. Nat Genet, 2019,51(3):481-493. doi: 10.1038/s41588-018-0321-7 pmid: 30804560
[21]	Sakornsakolpat P, Prokopenko D, Lamontagne M, Reeve NF, Guyatt AL, Jackson VE, Shrine N, Qiao DD, Bartz TM, Kim DK, Lee MK, Latourelle JC, Li XN, Morrow JD, Obeidat M, Wyss AB, Bakke P, Barr RG, Beaty TH, Belinsky SA, Brusselle GG, Crapo JD, de Jong K, DeMeo DL, Fingerlin TE, Gharib SA, Gulsvik A, Hall IP, Hokanson JE, Kim WJ, Lomas DA, London SJ, Meyers DA, O'Connor GT, Rennard SI, Schwartz DA, Sliwinski P, Sparrow D, Strachan DP, Tal-Singer R, Tesfaigzi Y, Vestbo J, Vonk JM, Yim JJ, Zhou X, Bosse Y, Manichaikul A, Lahousse L, Silverman EK, Boezen HM, Wain LV, Tobin MD, Hobbs BD, Cho MH,. Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations. Nat Genet, 2019,51(3):494-505. doi: 10.1038/s41588-018-0342-2 pmid: 30804561
[22]	Soler Artigas M, Wain LV, Repapi E, Obeidat M, Sayers I, Burton PR, Johnson T, Zhao JH, Albrecht E, Dominiczak AF, Kerr SM, Smith BH, Cadby G, Hui J, Palmer LJ, Hingorani AD, Wannamethee SG, Whincup PH, Ebrahim S, Smith GD, Barroso I, Loos RJ, Wareham NJ, Cooper C, Dennison E, Shaheen SO, Liu JZ, Marchini J, Medical Research Council National Survey of H, Development Respiratory Study T, Dahgam S, Naluai AT, Olin AC, Karrasch S, Heinrich J, Schulz H, McKeever TM, Pavord ID, Heliovaara M, Ripatti S, Surakka I, Blakey JD, Kahonen M, Britton JR, Nyberg F, Holloway JW, Lawlor DA, Morris RW, James AL, Jackson CM, Hall IP, Tobin MD, SpiroMeta C. Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function. Am J Respir Crit Care Med, 2011,184(7):786-795. doi: 10.1164/rccm.201102-0192OC pmid: 21965014
[23]	Castaldi PJ, Cho MH, Litonjua AA, Bakke P, Gulsvik A, Lomas DA, Anderson W, Beaty TH, Hokanson JE, Crapo JD, Laird N, Silverman EK . The association of genome-wide significant spirometric loci with chronic obstructive pulmonary disease susceptibility. Am J Respir Cell Mol Biol, 2011,45(6):1147-1153. doi: 10.1165/rcmb.2011-0055OC pmid: 21659657
[24]	Cho MH, McDonald MLN, Zhou XB, Mattheisen M, Castaldi PJ, Hersh CP, DeMeo DL, Sylvia JS, Ziniti J, Laird NM, Lange C, Litonjua AA, Sparrow D, Casaburi R, Barr RG, Regan EA, Make BJ, Hokanson JE, Lutz S, Dudenkov TM, Farzadegan H, Hetmanski JB, Tal-Singer R, Lomas DA, Bakke P, Gulsvik A, Crapo JD, Silverman EK, Beaty TH,. Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis. Lancet Respir Med, 2014,2(3):214-225. doi: 10.1016/S2213-2600(14)70002-5 pmid: 24621683
[25]	Lutz SM, Cho MH, Young K, Hersh CP, Castaldi PJ, McDonald ML, Regan E, Mattheisen M, DeMeo DL, Parker M, Foreman M, Make BJ, Jensen RL, Casaburi R, Lomas DA, Bhatt SP, Bakke P, Gulsvik A, Crapo JD, Beaty TH, Laird NM, Lange C, Hokanson JE, Silverman EK,. A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry. BMC Genet, 2015,16:138. doi: 10.1186/s12863-015-0299-4 pmid: 26634245
[26]	Dijkstra AE, Boezen HM, Van Den Berge M, Vonk JM, Hiemstra PS, Barr RG, Burkart KM, Manichaikul A, Pottinger TD, Silverman EK, Cho MH, Crapo JD, Beaty TH, Bakke P, Gulsvik A, Lomas DA, Bossé Y, Nickle DC, Paré PD, de Koning HJ, Lammers JW, Zanen P, Smolonska J, Wijmenga C, Brandsma CA, Groen HJM, Postma DS. Dissecting the genetics of chronic mucus hypersecretion in smokers with and without COPD. Eur Respir J, 2015,45(1):60-75. doi: 10.1183/09031936.00093314 pmid: 25234806
[27]	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, Lyytikainen LP, Granell R, Hysi PG, Flexeder C, Mahajan A, Beilby J, Bosse Y, Brandsma CA, Campbell H, Gieger C, Glaser S, Gonzalez JR, Grallert H, Hammond CJ, Harris SE, Hartikainen AL, Heliovaara M, Henderson J, Hocking L, Horikoshi M, Hutri-Kahonen N, Ingelsson E, Johansson A, Kemp JP, Kolcic I, Kumar A, Lind L, Melen E, Musk AW, Navarro P, Nickle DC, Padmanabhan S, Raitakari OT, Ried JS, Ripatti S, Schulz H, Scott RA, Sin DD, Starr JM, BiLEVE UK, Vinuela A, Volzke H, Wild SH, Wright AF, Zemunik T, Jarvis DL, Spector TD, Evans DM, Lehtimaki T, Vitart V, Kahonen 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. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation. Nat Commun, 2015,6:8658. doi: 10.1038/ncomms9658 pmid: 26635082
[28]	Wilk JB, Shrine NR, Loehr LR, Zhao JH, Manichaikul A, Lopez LM, Smith AV, Heckbert SR, Smolonska J, Tang W, Loth DW, Curjuric I, Hui J, Cho MH, Latourelle JC, Henry AP, Aldrich M, Bakke P, Beaty TH, Bentley AR, Borecki IB, Brusselle GG, Burkart KM, Chen TH, Couper D, Crapo JD, Davies G, Dupuis J, Franceschini N, Gulsvik A, Hancock DB, Harris TB, Hofman A, Imboden M, James AL, Khaw KT, Lahousse L, Launer LJ, Litonjua A, Liu Y, Lohman KK, Lomas DA, Lumley T, Marciante KD, McArdle WL, Meibohm B, Morrison AC, Musk AW, Myers RH, North KE, Postma DS, Psaty BM, Rich SS, Rivadeneira F, Rochat T, Rotter JI, Soler Artigas M, Starr JM, Uitterlinden AG, Wareham NJ, Wijmenga C, Zanen P, Province MA, Silverman EK, Deary IJ, Palmer LJ, Cassano PA, Gudnason V, Barr RG, Loos RJ, Strachan DP, London SJ, Boezen HM, Probst-Hensch N, Gharib SA, Hall IP, O'Connor GT, Tobin MD, Stricker BH. Genome wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction. Am J Respir Crit Care Med, 2012,186(7):622-632. doi: 10.1164/rccm.201202-0366OC pmid: 22837378
[29]	Burkart KM, Sofer T, London SJ, Manichaikul A, Hartwig FP, Yan Q, Soler Artigas M, Avila L, Chen W, Davis Thomas S, Diaz AA . A Genome-wide association study in Hispanics/Latinos identifies novel signals for lung function. The hispanic community health Study/Study of latinos. Am J Respir Crit Care Med, 2018,198(2):208-219. doi: 10.1164/rccm.201707-1493OC pmid: 29394082
[30]	Jackson VE, Latourelle JC, Wain LV, Smith AV, Grove ML, Bartz TM, Obeidat M, Province MA, Gao W, Qaiser B, Porteous DJ, Cassano PA, Ahluwalia TS, Grarup N, Li J, Altmaier E, Marten J, Harris SE, Manichaikul A, Pottinger TD, Li-Gao R, Lind-Thomsen A, Mahajan A, Lahousse L, Imboden M, Teumer A, Prins B, Lyytikäinen LP, Eiriksdottir G, Franceschini N, Sitlani CM, Brody JA, Bossé YT, Timens W, Kraja A, Loukola A, Tang WB, Liu YM, Bork-Jensen J, Justesen JM, Linneberg A, Lange LA, Rawal R, Karrasch S, Huffman JE, Smith BH, Davies G, Burkart KM, Mychaleckyj JC, Bonten TN, Enroth S, Lind L, Brusselle GG, Kumar A, Stubbe B, Kähönen M, Wyss AB, Psaty BM, Heckbert SR, Hao K, Rantanen T, Kritchevsky SB, Lohman K, Skaaby T, Pisinger C, Hansen T, Schulz H, Polasek O, Campbell A, Starr JM, Rich SS, Mook-Kanamori DO, Johansson Å, Ingelsson E, Uitterlinden A, Weiss S, Raitakari OT, Gudnason V, North KE, Gharib SA, Sin DD, Taylor KD, O'Connor GT, Kaprio J, Harris TB, Pederson O, Vestergaard H, Wilson JG, Strauch K, Hayward C, Kerr S, Deary IJ, Barr R, de Mutsert R, Gyllensten U, Morris AP, Ikram MA, Probst-Hensch N, Gläser S, Zeggini E, Lehtimäki T, Strachan DP, Dupuis J, Morrison AC, Hall IP, Tobin MD, London SJ. Meta-analysis of exome array data identifies six novel genetic loci for lung function. Wellcome Open Res, 2018,3:4. doi: 10.12688/wellcomeopenres.12583.3 pmid: 30175238
[31]	Morrow JD, Qiu WL, Chhabra D, Rennard SI, Belloni P, Belousov A, Pillai SG, Hersh CP . Identifying a gene expression signature of frequent COPD exacerbations in peripheral blood using network methods. BMC Med Genomics, 2015,8(1):1. doi: 10.1186/s12920-014-0072-y
[32]	Pillai SG, Ge DL, Zhu GH, Kong XY, Shianna KV, Need AC, Feng S, Hersh CP, Bakke P, Gulsvik A, Ruppert A, Lødrup Carlsen KC, Roses A, Anderson W, Rennard SI, Lomas DA, Silverman EK, Goldstein DB . A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genet, 2009,5(3):e1000421. doi: 10.1371/journal.pgen.1000421 pmid: 19300482
[33]	Cho MH, Boutaoui N, Klanderman BJ, Sylvia JS, Ziniti JP, Hersh CP, DeMeo DL, Hunninghake GM, Litonjua AA, Sparrow D, Lange C, Won S, Murphy JR, Beaty T, Regan EA, Make BJ, Hokanson JE, Crapo JD, Kong XQ, Anderson WH, Tal-Singer RM, Lomas DA, Bakke P, Gulsvik A, Pillai SG, Silverman EK. Variants in FAM13A are associated with chronic obstructive pulmonary disease. Nat Genet, 2010,42(3):200-202. doi: 10.1038/ng.535 pmid: 20173748
[34]	Van Durme YMTA, Eijgelsheim M, Joos GF, Hofman A, Uitterlinden AG, Brusselle GG, Stricker BHC . Hedgehog- interacting protein is a COPD susceptibility gene: the Rotterdam Study. Eur Respir J, 2010,36(1):89-95. doi: 10.1183/09031936.00129509 pmid: 19996190
[35]	Brehm JM, Hagiwara K, Tesfaigzi Y, Bruse S, Mariani TJ, Bhattacharya S, Boutaoui N, Ziniti JP, Soto-Quiros ME, Avila L, Cho MH, Himes B, Litonjua AA, Jacobson F, Bakke P, Gulsvik A, Anderson WH, Lomas DA, Forno E, Datta S, Silverman EK, Celedón JC . Identification of FGF7 as a novel susceptibility locus for chronic obstructive pulmonary disease. Thorax, 2011,66(12):1085-1090. doi: 10.1136/thoraxjnl-2011-200017
[36]	Cho MH, Castaldi PJ, Wan ES, Siedlinski M, Hersh CP, Demeo DL, Himes BE, Sylvia JS, Klanderman BJ, Ziniti JP, Lange C, Litonjua AA, Sparrow D, Regan EA, Make BJ, Hokanson JE, Murray T, Hetmanski JB, Pillai SG, Kong X, Anderson WH, Tal-Singer R, Lomas DA, Coxson HO, Edwards LD, MacNee W, Vestbo J, Yates JC, Agusti A, Calverley PM, Celli B, Crim C, Rennard S, Wouters E, Bakke P, Gulsvik A, Crapo JD, Beaty TH, Silverman EK,. A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. Hum Mol Genet, 2012,21(4):947-957. doi: 10.1093/hmg/ddr524
[37]	Hansel NN, Pare PD, Rafaels N, Sin DD, Sandford A, Daley D, Vergara C, Huang LL, Elliott WM, Pascoe CD, Arsenault BA, Postma DS, Boezen HM, Bossé Y, van den Berge M, Hiemstra PS, Cho MH, Litonjua AA, Sparrow D, Ober C, Wise RA, Connett J, Neptune ER, Beaty TH, Ruczinski I, Mathias RA, Barnes KC. Genome-wide association study identification of novel loci associated with airway responsiveness in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol, 2015,53(2):226-234. doi: 10.1165/rcmb.2014-0198OC pmid: 25514360
[38]	Hardin M, Cho M, McDonald ML, Beaty T, Ramsdell J, Bhatt S, Van Beek EJR, Make BJ, Crapo JD, Silverman EK, Hersh CP, . The clinical and genetic features of COPD- asthma overlap syndrome. Eur Respir J, 2014,44(2):341-350. doi: 10.1183/09031936.00216013
[39]	Lee JH, Cho MH, Hersh CP, McDonald MLN, Crapo JD, Bakke PS, Gulsvik A, Comellas AP, Wendt CH, Lomas DA, Kim V, Silverman EK,. Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease. Respir Res, 2014,15(1):113. doi: 10.1186/s12931-014-0113-2
[40]	Chen W, Brehm JM, Manichaikul A, Cho MH, Boutaoui N, Yan Q, Burkart KM, Enright PL, Rotter JI, Petersen H, Leng HG, Obeidat M, Bossé Y, Brandsma CA, Hao K, Rich SS, Powell R, Avila L, Soto-Quiros M, Silverman EK, Tesfaigzi Y, Barr RG, Celedón JC . A Genome-Wide Association Study of chronic obstructive pulmonary disease in Hispanics. Ann Am Thorac Soc, 2015,12(3):340-348. doi: 10.1513/AnnalsATS.201408-380OC pmid: 25584925
[41]	Hansel NN, Paré PD, Rafaels N, Sin DD, Sandford A, Daley D, Vergara C, Huang L, Elliott WM, Pascoe CD, Arsenault BA, Postma DS, Boezen HM, Bosse Y, van den Berge M, Hiemstra PS, Cho MH, Litonjua AA, Sparrow D, Ober C, Wise RA, Connett J, Neptune ER, Beaty TH, Ruczinski I, Mathias RA, Barnes KC,. Genome-Wide Association Study identification of novel loci associated with airway responsiveness in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol, 2015,53(2):226-234. doi: 10.1165/rcmb.2014-0198OC pmid: 25514360
[42]	McDonald ML, Cho MH, Sorheim IC, Lutz SM, Castaldi PJ, Lomas DA, Coxson HO, Edwards LD, MacNee W, Vestbo J, Yates JC, Agusti A, Calverley PM, Celli B, Crim C, Rennard SI, Wouters EF, Bakke P, Tal-Singer R, Miller BE, Gulsvik A, Casaburi R, Wells JM, Regan EA, Make BJ, Hokanson JE, Lange C, Crapo JD, Beaty TH, Silverman EK, Hersh CP . Common genetic variants associated with resting oxygenation in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol, 2014,51(5):678-687. doi: 10.1165/rcmb.2014-0135OC pmid: 24825563
[43]	Artigas MS, Wain LV, Shrine N, McKeever TM, BiLEVE U, Sayers I, Hall IP, Tobin MD,. Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls. PLoS One, 2017,12(1):e0170222.
[44]	Zhou XB, Qiu WL, Sathirapongsasuti JF, Cho MH, Mancini JD, Lao TT, Thibault DM, Litonjua AA, Bakke PS, Gulsvik A, Lomas DA, Beaty TH, Hersh CP, Anderson C, Geigenmuller U, Raby BA, Rennard SI, Perrella MA, Choi AMK, Quackenbush J, Silverman EK . Gene expression analysis uncovers novel hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells. Genomics, 2013,101(5):263-272. doi: 10.1016/j.ygeno.2013.02.010
[45]	Jiang ZQ, Lao TT, Qiu WL, Polverino F, Gupta K, Guo F, Mancini JD, Naing ZZC, Cho MH, Castaldi PJ, Sun Y, Yu J, Laucho-Contreras ME, Kobzik L, Raby BA, Choi AMK, Perrella MA, Owen CA, Silverman EK, Zhou XB . A chronic obstructive pulmonary disease susceptibility gene, FAM13A, regulates protein stability of β-catenin. Am J Respir Crit Care Med, 2016,194(2):185-197. doi: 10.1164/rccm.201505-0999OC pmid: 26862784
[46]	Jiang ZQ, Knudsen NH, Wang G, Qiu WL, Naing ZZC, Bai Y, Ai XB, Lee CH, Zhou XB . Genetic control of fatty acid β-oxidation in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol, 2017,56(6):738-748. doi: 10.1165/rcmb.2016-0282OC pmid: 28199134
[47]	Obeidat M, Miller S, Probert K, Billington CK, Henry AP, Hodge E, Nelson CP, Stewart CE, Swan C, Wain LV, Artigas MS, Melén E, Ushey K, Hao K, Lamontagne M, Bossé Y, Postma DS, Tobin MD, Sayers I, Hall IP . GSTCD and INTS12 regulation and expression in the human lung. PLoS One, 2013,8(9):e74630. doi: 10.1371/journal.pone.0074630 pmid: 24058608
[48]	Qian GQ, Yang NB, Shi JJ . Recent advances in nephronectin. Sheng Li Xue Bao, 2019,71(5):799-805. pmid: 31646334
[49]	Qian GQ, Henry A, Liu B, Miller S, Billington CK, Hall IP . Inhibition Of nephronectin expression In human bronchial epithelial cells using SiRNA knock-down. C71. Am J Respir Crit Care Med, 2016, A5866-A5866.
[50]	Hodge E, Nelson CP, Miller S, Billington CK, Stewart CE, Swan C, Malarstig A, Henry AP, Gowland C, Melén E, Hall IP, Sayers I . HTR4 gene structure and altered expression in the developing lung. Respir Res, 2013,14(1):77. doi: 10.1186/1465-9921-14-77
[51]	Miller S, Henry AP, Hodge E, Kheirallah AK, Billington CK, Rimington TL, Bhaker SK, Obeidat M, Melen E, Merid SK, Swan C, Gowland C, Nelson CP, Stewart CE, Bolton CE, Kilty I, Malarstig A, Parker SG, Moffatt MF, Wardlaw AJ, Hall IP, Sayers I . The Ser82 RAGE variant affects lung function and serum RAGE in smokers and sRAGE production in vitro. PLoS One, 2016,11(10):e0164041. doi: 10.1371/journal.pone.0164041 pmid: 27755550
[52]	Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, Fabbri LM, Goldin JG, Jones PW, MacNee W, Make BJ, Rabe KF, Rennard SI, Sciurba FC, Silverman EK, Vestbo J, Washko GR, Wouters EFM, Martinez FJ,. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med, 2010,182(5):598-604. doi: 10.1164/rccm.200912-1843CC pmid: 20522794
[53]	Thun GA, Imboden M, Ferrarotti I, Kumar A, Obeidat M, Zorzetto M, Haun M, Curjuric I, Couto Alves A, Jackson VE, Albrecht E, Ried JS, Teumer A, Lopez LM, Huffman JE, Enroth S, Bosse Y, Hao K, Timens W, Gyllensten U, Polasek O, Wilson JF, Rudan I, Hayward C, Sandford AJ, Deary IJ, Koch B, Reischl E, Schulz H, Hui J, James AL, Rochat T, Russi EW, Jarvelin MR, Strachan DP, Hall IP, Tobin MD, Dahl M, Fallgaard Nielsen S, Nordestgaard BG, Kronenberg F, Luisetti M, Probst-Hensch NM . Causal and synthetic associations of variants in the SERPINA gene cluster with alpha1-antitrypsin serum levels. PLoS Genet, 2013,9(8):e1003585. doi: 10.1371/journal.pgen.1003585 pmid: 23990791
[54]	Kong XY, Cho MH, Anderson W, Coxson HO, Muller N, Washko G, Hoffman EA, Bakke P, Gulsvik A, Lomas DA, Silverman EK, Pillai SG . Genome-wide association study identifies BICD1 as a susceptibility gene for emphysema. Am J Respir Crit Care Med, 2011,183(1):43-49. doi: 10.1164/rccm.201004-0541OC pmid: 20709820
[55]	Manichaikul A, Hoffman EA, Smolonska J, Gao W, Cho MH, Baumhauer H, Budoff M, Austin JHN, Washko GR, Carr JJ, Kaufman JD, Pottinger T, Powell CA, Wijmenga C, Zanen P, Groen HJM, Postma DS, Wanner A, Rouhani FN, Brantly ML, Powell R, Smith BM, Rabinowitz D, Raffel LJ, Hinckley Stukovsky KD, Crapo JD, Beaty TH, Hokanson JE, Silverman EK, Dupuis J, O’Connor GT, Boezen HM, Rich SS, Barr RG,. Genome-wide study of percent emphysema on computed tomography in the general population. The multi-ethnic study of atherosclerosis lung/SNP health association resource Study. Am J Respir Crit Care Med, 2014,189(4):408-418. doi: 10.1164/rccm.201306-1061OC pmid: 24383474
[56]	Cho MH, Castaldi PJ, Hersh CP, Hobbs BD, Barr RG, Tal-Singer R, Bakke P, Gulsvik A, San José Estépar R, Van Beek EJ, Coxson HO, Lynch DA, Washko GR, Laird NM, Crapo JD, Beaty TH, Silverma EK,. A genome-wide association study of emphysema and airway quantitative imaging phenotypes. Am J Respir Crit Care Med, 2015,192(5):559-569. doi: 10.1164/rccm.201501-0148OC pmid: 26030696
[57]	Dijkstra AE, Smolonska J, van den Berge M, Wijmenga C, Zanen P, Luinge MA, Platteel M, Lammers JW, Dahlback M, Tosh K, Benn M, Nielsen SF, Dahl M, Monique Verschuren W, Picavet HSJ, Smit HA, Owsijewitsch M, Kauczor HU, de Koning HJ, Nizankowska-Mogilnicka E, Mejza F, Nastalek P, van Diemen CC, Cho MH, Silverman EK, Crapo JD, Beaty TH, Lomas DA, Bakke P, Gulsvik A, Bossé Y, Obeidat MA, Loth DW, Lahousse L, Rivadeneira F, Uitterlinden AG, Hofman A, Stricker BH, Brusselle GG, van Duijn CM, Brouwer U, Koppelman GH, Vonk JM, Nawijn MC, Groen HJM, Timens W, Marike Boezen H, Postma DS. Susceptibility to chronic mucus hypersecretion, a genome wide association study. PLoS One, 2014,9(4):e91621. doi: 10.1371/journal.pone.0091621 pmid: 24714607
[58]	McDonald MN, Won S, Mattheisen M, Castaldi PJ, Cho MH, Rutten E, Hardin M, Yip WK, Rennard SI, Lomas DA, Wouters EFM, Agusti A, Casaburi R, Lange CP, O'Connor G, Hersh CP, Silverman EK . Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1. J Cachexia Sarcopenia Muscle, 2017,8(3):428-436. doi: 10.1002/jcsm.12171 pmid: 28044437
[59]	Lee JH, Cho MH, Hersh CP, McDonald ML, Wells JM, Dransfield MT, Bowler RP, Lynch DA, Lomas DA, Crapo JD, Silverman EK,. IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol, 2015,52(3):365-376. doi: 10.1165/rcmb.2014-0210OC pmid: 25101718
[60]	Shi JJ, Qian GQ, Yin FY, Li GX . Research progress in risk factors in female patients with chronic obstructive pulmonary disease. J Clin Pathol Res, 2018,32(6):1333-1336.
	石洁君, 钱国清, 尹凤英, 李国祥 . 女性慢性阻塞性肺疾病患者致病危险因素的研究进展. 临床与病理杂志, 2018,32(6):1333-1336.
[61]	Corvol H, Hodges CA, Drumm ML, Guillot L . Moving beyond genetics: is FAM13A a major biological contributor in lung physiology and chronic lung diseases? J Med Genet, 2014,51(10):646-649. doi: 10.1136/jmedgenet-2014-102525
[62]	熊明媚, 王健, 钟南山, 卢文菊 . 慢性阻塞性肺疾病相关基因组学研究. 中华结核和呼吸杂志, 2016,39(1):58-61.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

基因缩写	基因全称	位点
TRIP1	Eukaryotic translation initiation factor 3 subunit I	1p35.2
MFAP2	Microfibril associated protein 2	1p36.13
TNS1	Mensin 1	2q35
PID1	Phosphotyrosine interaction domain containing 1	2q36.3
HDAC4	Histone deacetylase 4	2q37.3
RARB	Retinoic acid receptor beta	3p24.2
EEFSEC	Eukaryotic elongation factor, selenocysteine-tRNA specific	3q21.3
FAM13A	Family with sequence similarity 13 member A	4q22.1
NPNT	Nephronectin	4q24
GSTCD	Glutathione S-transferase C-terminal domain containing	4q24
TET2	Tet methylcytosine dioxygenase 2	4q24
HHIP	Hedgehog interacting protein	4q31.21
HTR4	5-hydroxytryptamine receptor 4	5q32
ADAM19	ADAM Metallopeptidase Domain 19	5q33.3
NCR3	Natural cytotoxicity triggering receptor 3	6p21.33
AGER	Advanced glycosylation end-product specific receptor	6p21.32
ARMC2	Armadillo repeat containing 2	6q21
ZKSCAN3	Zinc finger with KRAB and SCAN domains 3	6p22.1
GPR126	Adhesion G protein-coupled receptor G6	6q24.2
ASTN2	Astrotactin 2	9q33.1
CDC123	Cell division cycle 123	10p14-p13
C10orf11	Leucine rich melanocyte differentiation associated	10q22.2-q22.3
CCDC38	Coiled-coil domain containing 38	12q23.1
RIN3	Ras and Rab interactor 3	14q32.12
THSD4	Thrombospondin type 1 domain containing 4	15q23
CFDP1	Craniofacial development protein 1	16q23.1
KCNE2	Potassium voltage-gated channel subfamily E regulatory subunit 2	21q22.11
MN1	MN1 proto-oncogene, transcriptional regulator	22q12.1

指标	指标全称(英文)	指标全称(中文)
ppfev1	Percent predicted FEV1 for latest exam	FEV1占预测值百分比
ppfvc	Percent predicted FVC for latest exam	FVC占预测值百分比
ppratio	Percent predicted FEV1/FVC for latest exam	FEV1/FVC占预测值百分比
ppfef	Percent predicted FEF25-75 for latest exam	FEF25-75占预测值百分比
ppfefrat	Percent predicted FEF25-75/FVC for latest exam	FEF25-75/FVC占预测值百分比
meanfev1	Mean FEV1 from two exams	FEV1均值
meanfvc	Mean FVC from two exams	FVC均值
meanratio	Mean FEV1/FVC from two exams	FEV1/FVC均值
Fev1slope	Longitudinal slope of FEV1	FEV1纵向斜率
fefslope	Longitudinal slope of FEV25-75	FEV25-75纵向斜率

基因	功能相关基因	基因	功能相关基因
DHDDS (3’-UTR)	HMGN2	NCOR1	ADORA2B, TTC19
NEXN	-	ASPSCR1	LRRC45
DENND2D^[21]	CEPT1, CHI3L2, DRAM2	C18orf8	-
C1orf54	MRPS21, RPRD2, ECM1	ZFP82	ZFP14
KRTCAP2	THBS4	MFAP2	-
RALGPS2	ANGPTL1	LOC101929516	PABPC4
LMOD1	SHISA4	TGFB2^[10,22~25]	-
ATAD2B	UBXN2A	TRAF3IP1	ASB1
PKDCC	-	SLMAP	-
ITGAV	-	RSRC1
SPATS2L	-	GSTCD^{[10,16,17,19,23]}	INTS12^[16,23]
C2orf54	-	NPNT^{[5,10,16,23,26,27]}	-
MIR548G	FILIP1L	AP3B1	-
BCHE	-	SPATA9^[22]	RHOBTB3
BTC	-	P4HA2-AS1	SLC22A5, P4HA2, C1QTNF5
LOC100996325	CEP72	CYFIP2	-
RNU6-71P	DST	ADAM19^[10,23,28]	-
JAZF1	-	DSP^[10]	-
MET	-	MIR588	CENPW
IER5L	CRAT, PPP2R4	GPR126^{[10,16,27,29]}	-
DOCK9	-	C1GALT1	-
CHAC1	INO80, CHP1, RAD51	QSOX2 (3’-UTR)	-
ATP2A3	-	DNLZ	SNAPC4, CARD9, INPP5E
PITPNM3	KIAA0753, TXNDC17	CDC123^[22]	NUDT5
TNFSF12-TNFSF13	TNFSF13, SENP3	MYPN	-
EML3	EEF1G, ROM1	SSH2	EFCAB5
ARHGEF17	FAM168A	FBXL20	CRKRS
RAB5B	CDK2	MAPT-AS1	LRRC37A4, MAPT
LRP1^[22]	-	TSEN54	CASKIN2
FGD6	-	LTBP4^[27]	-
RPAP1^[30]	ITPKA, LTK, TYRO3	ABHD12	PYGB
AAGAB	SMAD3, IQCH	UQCC1^[30]	GDF5
THSD4^[10,17,31]	-	SLC2A4RG	LIME1
IL27^[10]	SBK1, TUFM, CCDC101^[10], SULT1A1, SULT1A2, SH2B1, NPIPL1, CLN3, ATXN2L, EIF3C	SCARF2	-
MMP15

性状	基因	SNP名称	P值
FEV₁/FVC	MFAP2*	rs138641402	1.00E-04
FEV₁/FVC	LOC101929516 (intron) *	rs2070600	1.12E-04
FEV₁/FVC	CDC7/TGFBR3*	rs2045517	7.71E-04
FVC	SPAG17/TBX15*	rs7713065	6.39E-03
FEV₁/FVC	TGFB2*	rs993925	1.49E-02
FEV₁/FVC	CHRM3 (intron) *	rs4237643	2.62E-02
FEV₁	TNS1*	rs2283847	2.82E-02

慢性阻塞性肺疾病全基因组关联研究进展

Advances in genome-wide association study of chronic obstructive pulmonary disease

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 6

参考文献 62

相关文章 15

编辑推荐

Metrics

[1]	陈秀丽, 黄海燕, 吴强. 靶向敲除β-珠蛋白基因座控制区增强子HS2对K562细胞转录组的影响[J]. 遗传, 2022, 44(9): 783-797.
[2]	刘文兵, 刘丹, 闫进, 刘欣, 王前飞. 重症新型冠状病毒肺炎患者遗传易感性研究进展[J]. 遗传, 2022, 44(8): 672-681.
[3]	舒甜, 胡豪畅, 沈才杰, 林少沂, 陈晓敏. 肥厚型心肌病基因型-表型关联研究进展[J]. 遗传, 2022, 44(3): 198-207.
[4]	毛轲, 孟子秋, 张永彪. 神经嵴发育调控及颅面部遗传基础研究进展[J]. 遗传, 2022, 44(12): 1089-1102.
[5]	巴恒星, 胡鹏飞, 李春义. 鹿科动物基因组学研究进展[J]. 遗传, 2021, 43(4): 308-322.
[6]	李以格, 张丹丹. 后GWAS时代结直肠癌致病SNP功能机制的研究进展[J]. 遗传, 2021, 43(3): 203-214.
[7]	王娅洁, 吴爽爽, 储江, 孔祥阳. 肺部微生物组通过炎症反应介导慢性阻塞性肺疾病转化为肺癌的研究进展[J]. 遗传, 2021, 43(1): 30-39.
[8]	姜义圣,许执恒. 脑发育疾病及发病机制[J]. 遗传, 2019, 41(9): 801-815.
[9]	梁文权,侯豫,赵存友. 精神分裂症相关单核苷酸多态性调控microRNA功能研究进展[J]. 遗传, 2019, 41(8): 677-685.
[10]	黄莹,刘琪,池连江,石承民,吴祯,胡敏,石宏,陈华. BIG-Annotator：基因组测序数据高效功能注释及其在遗传诊断中的应用[J]. 遗传, 2018, 40(11): 1015-1023.
[11]	杨超, 杨瑞馥, 崔玉军. 细菌全基因组关联研究的方法与应用[J]. 遗传, 2018, 40(1): 57-65.
[12]	王钰嫣,王子兴,胡耀达,王蕾,李宁,张彪,韩伟,姜晶梅. 全基因组关联研究通路分析方法现状[J]. 遗传, 2017, 39(8): 707-716.
[13]	王翠翠,袁慧军. 高通量测序技术在遗传性耳聋研究中的应用及研究进展[J]. 遗传, 2017, 39(3): 208-219.
[14]	弓弦,张超,伊利亚斯·艾萨,时瑛,杨雪唯,努尔斯曼古丽奥斯曼,关亚群,徐书华. 2型糖尿病易感候选基因在世界不同人群中的多样性比较分析[J]. 遗传, 2016, 38(6): 543-559.
[15]	王海燕. 番茄果重数量性状基因的研究进展及在遗传学教学中的应用[J]. 遗传, 2015, 37(8): 837-844.