Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: A case control study in Caucasian patients

Minghua Wu, Shervin Assassi, Gloria A. Salazar, Claudia Pedroza, Olga Y. Gorlova, Wei V. Chen, Julio Charles, Miranda L. Taing, Kelley Liao, Fredrick Wigley, Laura Hummers, Ami Shah, Monique Hinchcliff, Dinesh Khanna, Elena Schiopu, Kristine Phillips, Daniel E. Furst, Virginia Steen, Murray Baron, Marie HudsonXiaodong Zhou, Janet Pope, Niall Jones, Peter Docherty, Nader A. Khalidi, David Robinson, Robert W. Simms, Richard M. Silver, Tracy M. Frech, Barri J. Fessler, Marvin J. Fritzler, Jerry A. Molitor, Barbara M. Segal, Malahat Movahedian, Javier Martín, John Varga, Maureen D. Mayes

Research output: Contribution to journalArticle

Abstract

Background: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc. Methods: A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and analyzed for their association with SSc. Results: We found an association of SSc with the SNP rs6793295 in the LRRC34 gene (OR = 1.14, CI 95 % 1.03 to 1.25, p value = 0.009) and rs11191865 in the OBFC1 gene (OR = 1.09, CI 95 % 1.00 to 1.19, p value = 0.043) in the discovery cohort. Additionally, rs7934606 in MUC2 (OR = 1.24, CI 95 % 1.01 to 1.52, p value = 0.037) was associated with SSc-ILD defined by imaging. However, these associations failed to replicate in the validation cohort. Furthermore, SNPs rs2076295 in DSP (β = -2.29, CI 95 % -3.85 to -0.74, p value = 0.004) rs17690703 in SPPL2C (β = 2.04, CI 95 % 0.21 to 3.88, p value = 0.029) and rs1981997 in MAPT (β = 2.26, CI 95 % 0.35 to 4.17, p value = 0.02) were associated with percent predicted forced vital capacity (FVC%) even after adjusting for the anti-topoisomerase (ATA)-positive subset. However, these associations also did not replicate in the validation cohort. Conclusions: Our results add new evidence that SSc and SSc-related ILD are genetically distinct from IIP, although they share phenotypic similarities.

Original languageEnglish (US)
Article number20
JournalArthritis Research and Therapy
Volume18
Issue number1
DOIs
StatePublished - Jan 20 2016

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Idiopathic Interstitial Pneumonias
Genetic Loci
Systemic Scleroderma
Genetic Predisposition to Disease
Case-Control Studies
Interstitial Lung Diseases
Single Nucleotide Polymorphism
Genome-Wide Association Study
Vital Capacity
Genes

Keywords

  • Genetic susceptibility
  • Idiopathic interstitial pneumonia (IIP)
  • SSc-ILD

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis : A case control study in Caucasian patients. / Wu, Minghua; Assassi, Shervin; Salazar, Gloria A.; Pedroza, Claudia; Gorlova, Olga Y.; Chen, Wei V.; Charles, Julio; Taing, Miranda L.; Liao, Kelley; Wigley, Fredrick; Hummers, Laura; Shah, Ami; Hinchcliff, Monique; Khanna, Dinesh; Schiopu, Elena; Phillips, Kristine; Furst, Daniel E.; Steen, Virginia; Baron, Murray; Hudson, Marie; Zhou, Xiaodong; Pope, Janet; Jones, Niall; Docherty, Peter; Khalidi, Nader A.; Robinson, David; Simms, Robert W.; Silver, Richard M.; Frech, Tracy M.; Fessler, Barri J.; Fritzler, Marvin J.; Molitor, Jerry A.; Segal, Barbara M.; Movahedian, Malahat; Martín, Javier; Varga, John; Mayes, Maureen D.

In: Arthritis Research and Therapy, Vol. 18, No. 1, 20, 20.01.2016.

Research output: Contribution to journalArticle

Wu, M, Assassi, S, Salazar, GA, Pedroza, C, Gorlova, OY, Chen, WV, Charles, J, Taing, ML, Liao, K, Wigley, F, Hummers, L, Shah, A, Hinchcliff, M, Khanna, D, Schiopu, E, Phillips, K, Furst, DE, Steen, V, Baron, M, Hudson, M, Zhou, X, Pope, J, Jones, N, Docherty, P, Khalidi, NA, Robinson, D, Simms, RW, Silver, RM, Frech, TM, Fessler, BJ, Fritzler, MJ, Molitor, JA, Segal, BM, Movahedian, M, Martín, J, Varga, J & Mayes, MD 2016, 'Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: A case control study in Caucasian patients', Arthritis Research and Therapy, vol. 18, no. 1, 20. https://doi.org/10.1186/s13075-016-0923-3
Wu, Minghua ; Assassi, Shervin ; Salazar, Gloria A. ; Pedroza, Claudia ; Gorlova, Olga Y. ; Chen, Wei V. ; Charles, Julio ; Taing, Miranda L. ; Liao, Kelley ; Wigley, Fredrick ; Hummers, Laura ; Shah, Ami ; Hinchcliff, Monique ; Khanna, Dinesh ; Schiopu, Elena ; Phillips, Kristine ; Furst, Daniel E. ; Steen, Virginia ; Baron, Murray ; Hudson, Marie ; Zhou, Xiaodong ; Pope, Janet ; Jones, Niall ; Docherty, Peter ; Khalidi, Nader A. ; Robinson, David ; Simms, Robert W. ; Silver, Richard M. ; Frech, Tracy M. ; Fessler, Barri J. ; Fritzler, Marvin J. ; Molitor, Jerry A. ; Segal, Barbara M. ; Movahedian, Malahat ; Martín, Javier ; Varga, John ; Mayes, Maureen D. / Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis : A case control study in Caucasian patients. In: Arthritis Research and Therapy. 2016 ; Vol. 18, No. 1.
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title = "Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: A case control study in Caucasian patients",
abstract = "Background: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc. Methods: A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and analyzed for their association with SSc. Results: We found an association of SSc with the SNP rs6793295 in the LRRC34 gene (OR = 1.14, CI 95 {\%} 1.03 to 1.25, p value = 0.009) and rs11191865 in the OBFC1 gene (OR = 1.09, CI 95 {\%} 1.00 to 1.19, p value = 0.043) in the discovery cohort. Additionally, rs7934606 in MUC2 (OR = 1.24, CI 95 {\%} 1.01 to 1.52, p value = 0.037) was associated with SSc-ILD defined by imaging. However, these associations failed to replicate in the validation cohort. Furthermore, SNPs rs2076295 in DSP (β = -2.29, CI 95 {\%} -3.85 to -0.74, p value = 0.004) rs17690703 in SPPL2C (β = 2.04, CI 95 {\%} 0.21 to 3.88, p value = 0.029) and rs1981997 in MAPT (β = 2.26, CI 95 {\%} 0.35 to 4.17, p value = 0.02) were associated with percent predicted forced vital capacity (FVC{\%}) even after adjusting for the anti-topoisomerase (ATA)-positive subset. However, these associations also did not replicate in the validation cohort. Conclusions: Our results add new evidence that SSc and SSc-related ILD are genetically distinct from IIP, although they share phenotypic similarities.",
keywords = "Genetic susceptibility, Idiopathic interstitial pneumonia (IIP), SSc-ILD",
author = "Minghua Wu and Shervin Assassi and Salazar, {Gloria A.} and Claudia Pedroza and Gorlova, {Olga Y.} and Chen, {Wei V.} and Julio Charles and Taing, {Miranda L.} and Kelley Liao and Fredrick Wigley and Laura Hummers and Ami Shah and Monique Hinchcliff and Dinesh Khanna and Elena Schiopu and Kristine Phillips and Furst, {Daniel E.} and Virginia Steen and Murray Baron and Marie Hudson and Xiaodong Zhou and Janet Pope and Niall Jones and Peter Docherty and Khalidi, {Nader A.} and David Robinson and Simms, {Robert W.} and Silver, {Richard M.} and Frech, {Tracy M.} and Fessler, {Barri J.} and Fritzler, {Marvin J.} and Molitor, {Jerry A.} and Segal, {Barbara M.} and Malahat Movahedian and Javier Mart{\'i}n and John Varga and Mayes, {Maureen D.}",
year = "2016",
month = "1",
day = "20",
doi = "10.1186/s13075-016-0923-3",
language = "English (US)",
volume = "18",
journal = "Arthritis Research and Therapy",
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}

TY - JOUR

T1 - Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis

T2 - A case control study in Caucasian patients

AU - Wu, Minghua

AU - Assassi, Shervin

AU - Salazar, Gloria A.

AU - Pedroza, Claudia

AU - Gorlova, Olga Y.

AU - Chen, Wei V.

AU - Charles, Julio

AU - Taing, Miranda L.

AU - Liao, Kelley

AU - Wigley, Fredrick

AU - Hummers, Laura

AU - Shah, Ami

AU - Hinchcliff, Monique

AU - Khanna, Dinesh

AU - Schiopu, Elena

AU - Phillips, Kristine

AU - Furst, Daniel E.

AU - Steen, Virginia

AU - Baron, Murray

AU - Hudson, Marie

AU - Zhou, Xiaodong

AU - Pope, Janet

AU - Jones, Niall

AU - Docherty, Peter

AU - Khalidi, Nader A.

AU - Robinson, David

AU - Simms, Robert W.

AU - Silver, Richard M.

AU - Frech, Tracy M.

AU - Fessler, Barri J.

AU - Fritzler, Marvin J.

AU - Molitor, Jerry A.

AU - Segal, Barbara M.

AU - Movahedian, Malahat

AU - Martín, Javier

AU - Varga, John

AU - Mayes, Maureen D.

PY - 2016/1/20

Y1 - 2016/1/20

N2 - Background: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc. Methods: A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and analyzed for their association with SSc. Results: We found an association of SSc with the SNP rs6793295 in the LRRC34 gene (OR = 1.14, CI 95 % 1.03 to 1.25, p value = 0.009) and rs11191865 in the OBFC1 gene (OR = 1.09, CI 95 % 1.00 to 1.19, p value = 0.043) in the discovery cohort. Additionally, rs7934606 in MUC2 (OR = 1.24, CI 95 % 1.01 to 1.52, p value = 0.037) was associated with SSc-ILD defined by imaging. However, these associations failed to replicate in the validation cohort. Furthermore, SNPs rs2076295 in DSP (β = -2.29, CI 95 % -3.85 to -0.74, p value = 0.004) rs17690703 in SPPL2C (β = 2.04, CI 95 % 0.21 to 3.88, p value = 0.029) and rs1981997 in MAPT (β = 2.26, CI 95 % 0.35 to 4.17, p value = 0.02) were associated with percent predicted forced vital capacity (FVC%) even after adjusting for the anti-topoisomerase (ATA)-positive subset. However, these associations also did not replicate in the validation cohort. Conclusions: Our results add new evidence that SSc and SSc-related ILD are genetically distinct from IIP, although they share phenotypic similarities.

AB - Background: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc. Methods: A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and analyzed for their association with SSc. Results: We found an association of SSc with the SNP rs6793295 in the LRRC34 gene (OR = 1.14, CI 95 % 1.03 to 1.25, p value = 0.009) and rs11191865 in the OBFC1 gene (OR = 1.09, CI 95 % 1.00 to 1.19, p value = 0.043) in the discovery cohort. Additionally, rs7934606 in MUC2 (OR = 1.24, CI 95 % 1.01 to 1.52, p value = 0.037) was associated with SSc-ILD defined by imaging. However, these associations failed to replicate in the validation cohort. Furthermore, SNPs rs2076295 in DSP (β = -2.29, CI 95 % -3.85 to -0.74, p value = 0.004) rs17690703 in SPPL2C (β = 2.04, CI 95 % 0.21 to 3.88, p value = 0.029) and rs1981997 in MAPT (β = 2.26, CI 95 % 0.35 to 4.17, p value = 0.02) were associated with percent predicted forced vital capacity (FVC%) even after adjusting for the anti-topoisomerase (ATA)-positive subset. However, these associations also did not replicate in the validation cohort. Conclusions: Our results add new evidence that SSc and SSc-related ILD are genetically distinct from IIP, although they share phenotypic similarities.

KW - Genetic susceptibility

KW - Idiopathic interstitial pneumonia (IIP)

KW - SSc-ILD

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