PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes

Bahram Namjou; Xana Kim-Howard; Celi Sun; Adam Adler; Sharon A. Chung; Kenneth M. Kaufman; Jennifer A. Kelly; Stuart B. Glenn; Joel M. Guthridge; Robert H. Scofield; Robert P. Kimberly; Elizabeth E. Brown; Graciela S. Alarcón; Jeffrey C. Edberg; Jae Hoon Kim; Jiyoung Choi; Rosalind Ramsey-Goldman; Michelle A. Petri; John D. Reveille; Luis M. Vilá; Susan A. Boackle; Barry I. Freedman; Betty P. Tsao; Carl D. Langefeld; Timothy J. Vyse; Chaim O. Jacob; Bernardo Pons-Estel; Timothy B. Niewold; Kathy L. Moser Sivils; Joan T. Merrill; Juan Manuel Anaya; Gary S. Gilkeson; Patrick M. Gaffney; Sang Cheol Bae; Marta E. Alarcón-Riquelme; John B. Harley; Lindsey A. Criswell; Judith A. James; Swapan K. Nath

doi:10.1371/journal.pone.0069404

PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes

Bahram Namjou, Xana Kim-Howard, Celi Sun, Adam Adler, Sharon A. Chung, Kenneth M. Kaufman, Jennifer A. Kelly, Stuart B. Glenn, Joel M. Guthridge, Robert H. Scofield, Robert P. Kimberly, Elizabeth E. Brown, Graciela S. Alarcón, Jeffrey C. Edberg, Jae Hoon Kim, Jiyoung Choi, Rosalind Ramsey-Goldman, Michelle A. Petri, John D. Reveille, Luis M. ViláSusan A. Boackle, Barry I. Freedman, Betty P. Tsao, Carl D. Langefeld, Timothy J. Vyse, Chaim O. Jacob, Bernardo Pons-Estel, Timothy B. Niewold, Kathy L. Moser Sivils, Joan T. Merrill, Juan Manuel Anaya, Gary S. Gilkeson, Patrick M. Gaffney, Sang Cheol Bae, Marta E. Alarcón-Riquelme, John B. Harley, Lindsey A. Criswell, Judith A. James, Swapan K. Nath

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

54 Citas (Scopus)

Resumen

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7×10^-9, OR = 1.40 (95% CI = 1.25-1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67-0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7×10^-5, OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs1217414 and rs3765598 may be associated with SLE. Further studies are required to confirm the involvement of rs2476601 with aCL IgG.

Idioma original	Inglés estadounidense
Número de artículo	e69404
Publicación	PLOS ONE
Volumen	8
N.º	8
DOI	https://doi.org/10.1371/journal.pone.0069404
Estado	Publicada - ago. 7 2013

Áreas temáticas de ASJC Scopus

Bioquímica, Genética y Biología Molecular General
Ciencias Agrícolas y Biológicas General
General

Acceder al documento

10.1371/journal.pone.0069404

Otros archivos y enlaces

Citar esto

Namjou, B., Kim-Howard, X., Sun, C., Adler, A., Chung, S. A., Kaufman, K. M., Kelly, J. A., Glenn, S. B., Guthridge, J. M., Scofield, R. H., Kimberly, R. P., Brown, E. E., Alarcón, G. S., Edberg, J. C., Kim, J. H., Choi, J., Ramsey-Goldman, R., Petri, M. A., Reveille, J. D., ... Nath, S. K. (2013). PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes. PLOS ONE, 8(8), Artículo e69404. https://doi.org/10.1371/journal.pone.0069404

@article{ff9bb210bf5f448b83158575118014a7,

title = "PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes",

abstract = "Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7×10-9, OR = 1.40 (95% CI = 1.25-1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67-0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7×10-5, OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs1217414 and rs3765598 may be associated with SLE. Further studies are required to confirm the involvement of rs2476601 with aCL IgG.",

author = "Bahram Namjou and Xana Kim-Howard and Celi Sun and Adam Adler and Chung, {Sharon A.} and Kaufman, {Kenneth M.} and Kelly, {Jennifer A.} and Glenn, {Stuart B.} and Guthridge, {Joel M.} and Scofield, {Robert H.} and Kimberly, {Robert P.} and Brown, {Elizabeth E.} and Alarc{\'o}n, {Graciela S.} and Edberg, {Jeffrey C.} and Kim, {Jae Hoon} and Jiyoung Choi and Rosalind Ramsey-Goldman and Petri, {Michelle A.} and Reveille, {John D.} and Vil{\'a}, {Luis M.} and Boackle, {Susan A.} and Freedman, {Barry I.} and Tsao, {Betty P.} and Langefeld, {Carl D.} and Vyse, {Timothy J.} and Jacob, {Chaim O.} and Bernardo Pons-Estel and Niewold, {Timothy B.} and {Moser Sivils}, {Kathy L.} and Merrill, {Joan T.} and Anaya, {Juan Manuel} and Gilkeson, {Gary S.} and Gaffney, {Patrick M.} and Bae, {Sang Cheol} and Alarc{\'o}n-Riquelme, {Marta E.} and Harley, {John B.} and Criswell, {Lindsey A.} and James, {Judith A.} and Nath, {Swapan K.}",

year = "2013",

month = aug,

day = "7",

doi = "10.1371/journal.pone.0069404",

language = "English (US)",

volume = "8",

journal = "PLOS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "8",

}

Namjou, B, Kim-Howard, X, Sun, C, Adler, A, Chung, SA, Kaufman, KM, Kelly, JA, Glenn, SB, Guthridge, JM, Scofield, RH, Kimberly, RP, Brown, EE, Alarcón, GS, Edberg, JC, Kim, JH, Choi, J, Ramsey-Goldman, R, Petri, MA, Reveille, JD, Vilá, LM, Boackle, SA, Freedman, BI, Tsao, BP, Langefeld, CD, Vyse, TJ, Jacob, CO, Pons-Estel, B, Niewold, TB, Moser Sivils, KL, Merrill, JT, Anaya, JM, Gilkeson, GS, Gaffney, PM, Bae, SC, Alarcón-Riquelme, ME, Harley, JB, Criswell, LA, James, JA & Nath, SK 2013, 'PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes', PLOS ONE, vol. 8, n.º 8, e69404. https://doi.org/10.1371/journal.pone.0069404

TY - JOUR

T1 - PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes

AU - Namjou, Bahram

AU - Kim-Howard, Xana

AU - Sun, Celi

AU - Adler, Adam

AU - Chung, Sharon A.

AU - Kaufman, Kenneth M.

AU - Kelly, Jennifer A.

AU - Glenn, Stuart B.

AU - Guthridge, Joel M.

AU - Scofield, Robert H.

AU - Kimberly, Robert P.

AU - Brown, Elizabeth E.

AU - Alarcón, Graciela S.

AU - Edberg, Jeffrey C.

AU - Kim, Jae Hoon

AU - Choi, Jiyoung

AU - Ramsey-Goldman, Rosalind

AU - Petri, Michelle A.

AU - Reveille, John D.

AU - Vilá, Luis M.

AU - Boackle, Susan A.

AU - Freedman, Barry I.

AU - Tsao, Betty P.

AU - Langefeld, Carl D.

AU - Vyse, Timothy J.

AU - Jacob, Chaim O.

AU - Pons-Estel, Bernardo

AU - Niewold, Timothy B.

AU - Moser Sivils, Kathy L.

AU - Merrill, Joan T.

AU - Anaya, Juan Manuel

AU - Gilkeson, Gary S.

AU - Gaffney, Patrick M.

AU - Bae, Sang Cheol

AU - Alarcón-Riquelme, Marta E.

AU - Harley, John B.

AU - Criswell, Lindsey A.

AU - James, Judith A.

AU - Nath, Swapan K.

PY - 2013/8/7

Y1 - 2013/8/7

N2 - Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7×10-9, OR = 1.40 (95% CI = 1.25-1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67-0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7×10-5, OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs1217414 and rs3765598 may be associated with SLE. Further studies are required to confirm the involvement of rs2476601 with aCL IgG.

AB - Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7×10-9, OR = 1.40 (95% CI = 1.25-1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67-0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7×10-5, OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs1217414 and rs3765598 may be associated with SLE. Further studies are required to confirm the involvement of rs2476601 with aCL IgG.

UR - http://www.scopus.com/inward/record.url?scp=84881329854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881329854&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0069404

DO - 10.1371/journal.pone.0069404

M3 - Article

C2 - 23950893

AN - SCOPUS:84881329854

SN - 1932-6203

VL - 8

JO - PLOS ONE

JF - PLOS ONE

IS - 8

M1 - e69404

ER -

PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes

Resumen

Áreas temáticas de ASJC Scopus

Acceder al documento

Otros archivos y enlaces

Huella

Citar esto