Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus

Elena Sanchez, Ajay Nadig, Bruce C. Richardson, Barry I. Freedman, Kenneth M. Kaufman, Jennifer A. Kelly, Timothy B. Niewold, Diane L. Kamen, Gary S. Gilkeson, Julie T. Ziegler, Carl D. Langefeld, Graciela S. Alarcón, Jeffrey C. Edberg, Rosalind Ramsey-Goldman, Michelle Petri, Elizabeth E. Brown, Robert P. Kimberly, John D. Reveille, Luis M. Vilá, Joan T. Merrill & 16 otros Juan Manuel Anaya, Judith A. James, Bernardo A. Pons-Estel, Javier Martin, So Yeon Park, So Young Bang, Sang Cheol Bae, Kathy L. Moser, Timothy J. Vyse, Lindsey A. Criswell, Patrick M. Gaffney, Betty P. Tsao, Chaim O. Jacob, John B. Harley, Marta E. Alarcón-Riquelme, Amr H. Sawalha

Resultado de la investigación: Contribución a RevistaArtículo

71 Citas (Scopus)

Resumen

Objective: Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. Materials and methods: 4001 European-derived, 547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Results: Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0 × 10-6, OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of
Idioma originalEnglish (US)
Páginas (desde-hasta)1752-1757
Número de páginas6
PublicaciónAnnals of the Rheumatic Diseases
DOI
EstadoPublished - oct 1 2011

Huella dactilar

Genetic Loci
Genetic Predisposition to Disease
Systemic Lupus Erythematosus
Alleles
Exanthema
Oral Ulcer
Hispanic Americans
African Americans
Autoimmune Diseases
Kidney

Citar esto

Sanchez, E., Nadig, A., Richardson, B. C., Freedman, B. I., Kaufman, K. M., Kelly, J. A., ... Sawalha, A. H. (2011). Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus. Annals of the Rheumatic Diseases, 1752-1757. https://doi.org/10.1136/ard.2011.154104
Sanchez, Elena ; Nadig, Ajay ; Richardson, Bruce C. ; Freedman, Barry I. ; Kaufman, Kenneth M. ; Kelly, Jennifer A. ; Niewold, Timothy B. ; Kamen, Diane L. ; Gilkeson, Gary S. ; Ziegler, Julie T. ; Langefeld, Carl D. ; Alarcón, Graciela S. ; Edberg, Jeffrey C. ; Ramsey-Goldman, Rosalind ; Petri, Michelle ; Brown, Elizabeth E. ; Kimberly, Robert P. ; Reveille, John D. ; Vilá, Luis M. ; Merrill, Joan T. ; Anaya, Juan Manuel ; James, Judith A. ; Pons-Estel, Bernardo A. ; Martin, Javier ; Park, So Yeon ; Bang, So Young ; Bae, Sang Cheol ; Moser, Kathy L. ; Vyse, Timothy J. ; Criswell, Lindsey A. ; Gaffney, Patrick M. ; Tsao, Betty P. ; Jacob, Chaim O. ; Harley, John B. ; Alarcón-Riquelme, Marta E. ; Sawalha, Amr H. / Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus. En: Annals of the Rheumatic Diseases. 2011 ; pp. 1752-1757.
@article{5c1e69ae1bdc432f8cd2ce7c1a30324b,
title = "Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus",
abstract = "Objective: Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. Materials and methods: 4001 European-derived, 547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Results: Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0 × 10-6, OR 1.25, 95{\%} CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95{\%} CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95{\%} CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95{\%} CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95{\%} CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95{\%} CI 1.04 to 1.22). All these associations are significant with a false discovery rate of",
author = "Elena Sanchez and Ajay Nadig and Richardson, {Bruce C.} and Freedman, {Barry I.} and Kaufman, {Kenneth M.} and Kelly, {Jennifer A.} and Niewold, {Timothy B.} and Kamen, {Diane L.} and Gilkeson, {Gary S.} and Ziegler, {Julie T.} and Langefeld, {Carl D.} and Alarc{\'o}n, {Graciela S.} and Edberg, {Jeffrey C.} and Rosalind Ramsey-Goldman and Michelle Petri and Brown, {Elizabeth E.} and Kimberly, {Robert P.} and Reveille, {John D.} and Vil{\'a}, {Luis M.} and Merrill, {Joan T.} and Anaya, {Juan Manuel} and James, {Judith A.} and Pons-Estel, {Bernardo A.} and Javier Martin and Park, {So Yeon} and Bang, {So Young} and Bae, {Sang Cheol} and Moser, {Kathy L.} and Vyse, {Timothy J.} and Criswell, {Lindsey A.} and Gaffney, {Patrick M.} and Tsao, {Betty P.} and Jacob, {Chaim O.} and Harley, {John B.} and Alarc{\'o}n-Riquelme, {Marta E.} and Sawalha, {Amr H.}",
year = "2011",
month = "10",
day = "1",
doi = "10.1136/ard.2011.154104",
language = "English (US)",
pages = "1752--1757",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",

}

Sanchez, E, Nadig, A, Richardson, BC, Freedman, BI, Kaufman, KM, Kelly, JA, Niewold, TB, Kamen, DL, Gilkeson, GS, Ziegler, JT, Langefeld, CD, Alarcón, GS, Edberg, JC, Ramsey-Goldman, R, Petri, M, Brown, EE, Kimberly, RP, Reveille, JD, Vilá, LM, Merrill, JT, Anaya, JM, James, JA, Pons-Estel, BA, Martin, J, Park, SY, Bang, SY, Bae, SC, Moser, KL, Vyse, TJ, Criswell, LA, Gaffney, PM, Tsao, BP, Jacob, CO, Harley, JB, Alarcón-Riquelme, ME & Sawalha, AH 2011, 'Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus', Annals of the Rheumatic Diseases, pp. 1752-1757. https://doi.org/10.1136/ard.2011.154104

Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus. / Sanchez, Elena; Nadig, Ajay; Richardson, Bruce C.; Freedman, Barry I.; Kaufman, Kenneth M.; Kelly, Jennifer A.; Niewold, Timothy B.; Kamen, Diane L.; Gilkeson, Gary S.; Ziegler, Julie T.; Langefeld, Carl D.; Alarcón, Graciela S.; Edberg, Jeffrey C.; Ramsey-Goldman, Rosalind; Petri, Michelle; Brown, Elizabeth E.; Kimberly, Robert P.; Reveille, John D.; Vilá, Luis M.; Merrill, Joan T.; Anaya, Juan Manuel; James, Judith A.; Pons-Estel, Bernardo A.; Martin, Javier; Park, So Yeon; Bang, So Young; Bae, Sang Cheol; Moser, Kathy L.; Vyse, Timothy J.; Criswell, Lindsey A.; Gaffney, Patrick M.; Tsao, Betty P.; Jacob, Chaim O.; Harley, John B.; Alarcón-Riquelme, Marta E.; Sawalha, Amr H.

En: Annals of the Rheumatic Diseases, 01.10.2011, p. 1752-1757.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus

AU - Sanchez, Elena

AU - Nadig, Ajay

AU - Richardson, Bruce C.

AU - Freedman, Barry I.

AU - Kaufman, Kenneth M.

AU - Kelly, Jennifer A.

AU - Niewold, Timothy B.

AU - Kamen, Diane L.

AU - Gilkeson, Gary S.

AU - Ziegler, Julie T.

AU - Langefeld, Carl D.

AU - Alarcón, Graciela S.

AU - Edberg, Jeffrey C.

AU - Ramsey-Goldman, Rosalind

AU - Petri, Michelle

AU - Brown, Elizabeth E.

AU - Kimberly, Robert P.

AU - Reveille, John D.

AU - Vilá, Luis M.

AU - Merrill, Joan T.

AU - Anaya, Juan Manuel

AU - James, Judith A.

AU - Pons-Estel, Bernardo A.

AU - Martin, Javier

AU - Park, So Yeon

AU - Bang, So Young

AU - Bae, Sang Cheol

AU - Moser, Kathy L.

AU - Vyse, Timothy J.

AU - Criswell, Lindsey A.

AU - Gaffney, Patrick M.

AU - Tsao, Betty P.

AU - Jacob, Chaim O.

AU - Harley, John B.

AU - Alarcón-Riquelme, Marta E.

AU - Sawalha, Amr H.

PY - 2011/10/1

Y1 - 2011/10/1

N2 - Objective: Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. Materials and methods: 4001 European-derived, 547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Results: Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0 × 10-6, OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of

AB - Objective: Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. Materials and methods: 4001 European-derived, 547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Results: Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0 × 10-6, OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of

U2 - 10.1136/ard.2011.154104

DO - 10.1136/ard.2011.154104

M3 - Article

SP - 1752

EP - 1757

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

ER -