Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin

Paula Tejera, Nuala J. Meyer, Feng Chen, Rui Feng, Yang Zhao, D. Shane O'Mahony, Lin Li, Chau Chyun Sheu, Rihong Zhai, Zhaoxi Wang, Li Su, Ed Bajwa, Amy M. Ahasic, Peter F. Clardy, Michelle Ng Gong, Angela J. Frank, Paul N. Lanken, B. Taylor Thompson, Jason D. Christie, Mark M. Wurfel & 2 others Grant E. O'Keefe, David C. Christiani

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: The role of genetics in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) from direct or indirect lung injury has not been specifically investigated. The aim of this study was to identify genetic variants contributing to ALI/ARDS from pulmonary or extrapulmonary causes. Methods: We conducted a multistage genetic association study. We first performed a large-scale genotyping (50K ITMAT-Broad_CARe Chip) in 1717 critically ill Caucasian patients with either pulmonary or extrapulmonary injury, to identify single nucleotide polymorphisms (SNPs) associated with the development of ARDS from direct or indirect insults to the lung. Identified SNPs (p≤0.0005) were validated in two separated populations (Stage II), with trauma (Population I; n=765) and pneumonia/pulmonary sepsis (Population II; n=838), as causes for ALI/ARDS. Genetic variants replicating their association with trauma related-ALI in Stage II were validated in a second traumaassociated ALI population (n=224, Stage III). Results: In Stage I, non-overlapping SNPs were significantly associated with ARDS from direct/indirect lung injury, respectively. The association between rs1190286 (POPDC3) and reduced risk of ARDS from pulmonary injury was validated in Stage II (p<0.003). SNP rs324420 (FAAH) was consistently associated with increased risk of ARDS from extrapulmonary causes in two independent ALI-trauma populations (p<0.006, Stage II; p<0.05, Stage III). Meta-analysis confirmed these associations. Conclusions: Different genetic variants may influence ARDS susceptibility depending on direct versus indirect insults. Functional SNPs in POPDC3 and FAAH genes may be driving the association with direct and indirect ALI/ARDS, respectively.

Original languageEnglish (US)
Pages (from-to)671-680
Number of pages10
JournalJournal of Medical Genetics
Volume49
Issue number11
DOIs
StatePublished - Nov 2012

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Adult Respiratory Distress Syndrome
Acute Lung Injury
Lung
Single Nucleotide Polymorphism
Lung Injury
Population
Wounds and Injuries
Genetic Association Studies
Critical Illness
Meta-Analysis
Sepsis
Pneumonia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin. / Tejera, Paula; Meyer, Nuala J.; Chen, Feng; Feng, Rui; Zhao, Yang; O'Mahony, D. Shane; Li, Lin; Sheu, Chau Chyun; Zhai, Rihong; Wang, Zhaoxi; Su, Li; Bajwa, Ed; Ahasic, Amy M.; Clardy, Peter F.; Gong, Michelle Ng; Frank, Angela J.; Lanken, Paul N.; Thompson, B. Taylor; Christie, Jason D.; Wurfel, Mark M.; O'Keefe, Grant E.; Christiani, David C.

In: Journal of Medical Genetics, Vol. 49, No. 11, 11.2012, p. 671-680.

Research output: Contribution to journalArticle

Tejera, P, Meyer, NJ, Chen, F, Feng, R, Zhao, Y, O'Mahony, DS, Li, L, Sheu, CC, Zhai, R, Wang, Z, Su, L, Bajwa, E, Ahasic, AM, Clardy, PF, Gong, MN, Frank, AJ, Lanken, PN, Thompson, BT, Christie, JD, Wurfel, MM, O'Keefe, GE & Christiani, DC 2012, 'Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin', Journal of Medical Genetics, vol. 49, no. 11, pp. 671-680. https://doi.org/10.1136/jmedgenet-2012-100972
Tejera, Paula ; Meyer, Nuala J. ; Chen, Feng ; Feng, Rui ; Zhao, Yang ; O'Mahony, D. Shane ; Li, Lin ; Sheu, Chau Chyun ; Zhai, Rihong ; Wang, Zhaoxi ; Su, Li ; Bajwa, Ed ; Ahasic, Amy M. ; Clardy, Peter F. ; Gong, Michelle Ng ; Frank, Angela J. ; Lanken, Paul N. ; Thompson, B. Taylor ; Christie, Jason D. ; Wurfel, Mark M. ; O'Keefe, Grant E. ; Christiani, David C. / Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin. In: Journal of Medical Genetics. 2012 ; Vol. 49, No. 11. pp. 671-680.
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abstract = "Background: The role of genetics in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) from direct or indirect lung injury has not been specifically investigated. The aim of this study was to identify genetic variants contributing to ALI/ARDS from pulmonary or extrapulmonary causes. Methods: We conducted a multistage genetic association study. We first performed a large-scale genotyping (50K ITMAT-Broad_CARe Chip) in 1717 critically ill Caucasian patients with either pulmonary or extrapulmonary injury, to identify single nucleotide polymorphisms (SNPs) associated with the development of ARDS from direct or indirect insults to the lung. Identified SNPs (p≤0.0005) were validated in two separated populations (Stage II), with trauma (Population I; n=765) and pneumonia/pulmonary sepsis (Population II; n=838), as causes for ALI/ARDS. Genetic variants replicating their association with trauma related-ALI in Stage II were validated in a second traumaassociated ALI population (n=224, Stage III). Results: In Stage I, non-overlapping SNPs were significantly associated with ARDS from direct/indirect lung injury, respectively. The association between rs1190286 (POPDC3) and reduced risk of ARDS from pulmonary injury was validated in Stage II (p<0.003). SNP rs324420 (FAAH) was consistently associated with increased risk of ARDS from extrapulmonary causes in two independent ALI-trauma populations (p<0.006, Stage II; p<0.05, Stage III). Meta-analysis confirmed these associations. Conclusions: Different genetic variants may influence ARDS susceptibility depending on direct versus indirect insults. Functional SNPs in POPDC3 and FAAH genes may be driving the association with direct and indirect ALI/ARDS, respectively.",
author = "Paula Tejera and Meyer, {Nuala J.} and Feng Chen and Rui Feng and Yang Zhao and O'Mahony, {D. Shane} and Lin Li and Sheu, {Chau Chyun} and Rihong Zhai and Zhaoxi Wang and Li Su and Ed Bajwa and Ahasic, {Amy M.} and Clardy, {Peter F.} and Gong, {Michelle Ng} and Frank, {Angela J.} and Lanken, {Paul N.} and Thompson, {B. Taylor} and Christie, {Jason D.} and Wurfel, {Mark M.} and O'Keefe, {Grant E.} and Christiani, {David C.}",
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T1 - Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin

AU - Tejera, Paula

AU - Meyer, Nuala J.

AU - Chen, Feng

AU - Feng, Rui

AU - Zhao, Yang

AU - O'Mahony, D. Shane

AU - Li, Lin

AU - Sheu, Chau Chyun

AU - Zhai, Rihong

AU - Wang, Zhaoxi

AU - Su, Li

AU - Bajwa, Ed

AU - Ahasic, Amy M.

AU - Clardy, Peter F.

AU - Gong, Michelle Ng

AU - Frank, Angela J.

AU - Lanken, Paul N.

AU - Thompson, B. Taylor

AU - Christie, Jason D.

AU - Wurfel, Mark M.

AU - O'Keefe, Grant E.

AU - Christiani, David C.

PY - 2012/11

Y1 - 2012/11

N2 - Background: The role of genetics in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) from direct or indirect lung injury has not been specifically investigated. The aim of this study was to identify genetic variants contributing to ALI/ARDS from pulmonary or extrapulmonary causes. Methods: We conducted a multistage genetic association study. We first performed a large-scale genotyping (50K ITMAT-Broad_CARe Chip) in 1717 critically ill Caucasian patients with either pulmonary or extrapulmonary injury, to identify single nucleotide polymorphisms (SNPs) associated with the development of ARDS from direct or indirect insults to the lung. Identified SNPs (p≤0.0005) were validated in two separated populations (Stage II), with trauma (Population I; n=765) and pneumonia/pulmonary sepsis (Population II; n=838), as causes for ALI/ARDS. Genetic variants replicating their association with trauma related-ALI in Stage II were validated in a second traumaassociated ALI population (n=224, Stage III). Results: In Stage I, non-overlapping SNPs were significantly associated with ARDS from direct/indirect lung injury, respectively. The association between rs1190286 (POPDC3) and reduced risk of ARDS from pulmonary injury was validated in Stage II (p<0.003). SNP rs324420 (FAAH) was consistently associated with increased risk of ARDS from extrapulmonary causes in two independent ALI-trauma populations (p<0.006, Stage II; p<0.05, Stage III). Meta-analysis confirmed these associations. Conclusions: Different genetic variants may influence ARDS susceptibility depending on direct versus indirect insults. Functional SNPs in POPDC3 and FAAH genes may be driving the association with direct and indirect ALI/ARDS, respectively.

AB - Background: The role of genetics in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) from direct or indirect lung injury has not been specifically investigated. The aim of this study was to identify genetic variants contributing to ALI/ARDS from pulmonary or extrapulmonary causes. Methods: We conducted a multistage genetic association study. We first performed a large-scale genotyping (50K ITMAT-Broad_CARe Chip) in 1717 critically ill Caucasian patients with either pulmonary or extrapulmonary injury, to identify single nucleotide polymorphisms (SNPs) associated with the development of ARDS from direct or indirect insults to the lung. Identified SNPs (p≤0.0005) were validated in two separated populations (Stage II), with trauma (Population I; n=765) and pneumonia/pulmonary sepsis (Population II; n=838), as causes for ALI/ARDS. Genetic variants replicating their association with trauma related-ALI in Stage II were validated in a second traumaassociated ALI population (n=224, Stage III). Results: In Stage I, non-overlapping SNPs were significantly associated with ARDS from direct/indirect lung injury, respectively. The association between rs1190286 (POPDC3) and reduced risk of ARDS from pulmonary injury was validated in Stage II (p<0.003). SNP rs324420 (FAAH) was consistently associated with increased risk of ARDS from extrapulmonary causes in two independent ALI-trauma populations (p<0.006, Stage II; p<0.05, Stage III). Meta-analysis confirmed these associations. Conclusions: Different genetic variants may influence ARDS susceptibility depending on direct versus indirect insults. Functional SNPs in POPDC3 and FAAH genes may be driving the association with direct and indirect ALI/ARDS, respectively.

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