Polygenic risk scores identify heterogeneity in asthma and chronic obstructive pulmonary disease

被引：7

作者：

Moll, Matthew ^{[1
,2
]}

Sordillo, Joanne E. ^{[3
,4
]}

Ghosh, Auyon J. ^{[5
]}

Hayden, Lystra P. ^{[6
]}

McDermott, Gregory ^{[7
]}

McGeachie, Michael J.

Dahlin, Amber

Tiwari, Anshul ^{[8
]}

Manmadkar, Monica G. ^{[8
]}

Abston, Eric D. ^{[9
]}

Pavuluri, Chandan ^{[1
,2
]}

Saferali, Aabida ^{[2
,8
]}

Begum, Sofina ^{[2
,8
]}

Ziniti, John P. ^{[2
,8
]}

Gulsvik, Amund ^{[10
]}

Bakke, Per S. ^{[10
]}

Aschard, Hugues ^{[11
]}

Iribarren, Carlos ^{[12
]}

Hersh, Craig P. ^{[1
,2
]}

Sparks, Jeffrey A. ^{[2
,7
]}

Hobbs, Brian D. ^{[1
,2
]}

Lasky-Su, Jessica A. ^{[2
,8
]}

Silverman, Edwin K. ^{[2
,8
]}

Weiss, Scott T. ^{[2
,8
]}

Wu, Ann Chen ^{[3
,4
]}

Cho, Michael H. ^{[1
,2
,13
]}

机构：

[1] Harvard Med Sch, Dept Med, Channing Div Network Med, Div Pulm & Crit Care Med, Boston, MA USA

[2] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA

[3] PRecis Med Translat Res PROMoTeR Ctr, Harvard Med Sch, Dept Populat Med, Boston, MA USA

[4] Harvard Pilgrim Hlth Care, Boston, MA USA

[5] SUNY Upstate Med Ctr, Dept Med, Div Pulm & Crit Care Med, Syracuse, NY USA

[6] Harvard Med Sch, Boston Childrens Hosp, Dept Pediat, Div Pulm Med, Boston, MA USA

[7] Brigham & Womens Hosp, Dept Med, Div Rheumatol Inflammat & Immun, Boston, MA USA

[8] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA USA

[9] Massachusetts Gen Hosp, Dept Surg, Boston, MA USA

[10] Univ Bergen, Dept Clin Sci, Bergen, Norway

[11] Univ Paris, Inst Pasteur, Dept Computat Biol, Paris, France

[12] Kaiser Permanente Northern Calif, Div Res, Oakland, ON, Canada

[13] Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2023年 / 152卷 / 06期

基金：

美国国家卫生研究院;

关键词：

Asthma; chronic obstructive pulmonary disease; asthma-COPD overlap; polygenic risk scores; heterogeneity; GENETIC EPIDEMIOLOGY RESEARCH; LUNG-FUNCTION; ADULT HEALTH; COPD; OVERLAP; ASSOCIATIONS; INFORMATICS; REGRESSION; LOCI;

D O I：

10.1016/j.jaci.2023.08.002

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: Asthma and chronic obstructive pulmonary disease (COPD) have distinct and overlapping genetic and clinical features. Objective: We sought to test the hypothesis that polygenic risk scores (PRSs) for asthma (PRSAsthma) and spirometry (FEV1 and FEV1/forced vital capacity; PRSspiro) would demonstrate differential associations with asthma, COPD, and asthma-COPD overlap (ACO). Methods: We developed and tested 2 asthma PRSs and applied the higher performing PRSAsthma and a previously published PRSspiro to research (Genetic Epidemiology of COPD study and Childhood Asthma Management Program, with spirometry) and electronic health record-based (Mass General Brigham Biobank and Genetic Epidemiology Research on Adult Health and Aging [GERA]) studies. We assessed the association of PRSs with COPD and asthma using modified random-effects and binary-effects meta-analyses, and ACO and asthma exacerbations in specific cohorts. Models were adjusted for confounders and genetic ancestry. Results: In meta-analyses of 102,477 participants, the PRSAsthma (odds ratio [OR] per SD, 1.16 [95% CI, 1.14-1.19]) and PRSspiro (OR per SD, 1.19 [95% CI, 1.17-1.22]) both predicted asthma, whereas the PRSspiro predicted COPD (OR per SD, 1.25 [95% CI, 1.21-1.30]). However, results differed by cohort. The PRSspiro was not associated with COPD in GERA and Mass General Brigham Biobank. In the Genetic Epidemiology of COPD study, the PRSAsthma (OR per SD: Whites, 1.3; African Americans, 1.2) and PRSspiro (OR per SD: Whites, 2.2; African Americans, 1.6) were both associated with ACO. In GERA, the PRSAsthma was associated with asthma exacerbations (OR, 1.18) in Whites; the PRSspiro was associated with asthma exacerbations in White, LatinX, and East Asian participants. Conclusions: PRSs for asthma and spirometry are both associated with ACO and asthma exacerbations. Genetic prediction performance differs in research versus electronic health record- based cohorts. (J Allergy Clin Immunol 2023;152:1423-32.)

引用

页码：1423 / 1432

页数：10

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