Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study

Elena Sánchez, Mary E. Comeau, Barry I. Freedman, Jennifer A. Kelly, Kenneth M. Kaufman, Carl D. Langefeld, Elizabeth E. Brown, Graciela S. Alarcón, Robert P. Kimberly, Jeffrey C. Edberg, Rosalind Ramsey-Goldman, Michelle Petri, John D. Reveille, Luis M. Vilá, Joan T. Merrill, Betty P. Tsao, Diane L. Kamen, Gary S. Gilkeson, Judith A. James, Timothy J. VysePatrick M. Gaffney, Chaim O. Jacob, Timothy B. Niewold, Bruce C. Richardson, John B. Harley, Marta E. Alarcón-Riquelme, Amr H. Sawalha

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Objective Candidate gene and genome-wide association studies have identified several disease susceptibility loci in lupus patients. These studies have largely been performed in lupus patients who are Asian or of European ancestry. This study was undertaken to examine whether some of these same susceptibility loci increase lupus risk in African American individuals. Methods Single-nucleotide polymorphisms tagging 15 independent lupus susceptibility loci were genotyped in a set of 1,724 lupus patients and 2,024 healthy controls of African American descent. The loci examined included PTPN22, FCGR2A, TNFSF4, STAT4, CTLA4, PDCD1, PXK, BANK1, MSH5 (HLA region), CFB (HLA region), C8orf13-BLK region, MBL2, KIAA1542, ITGAM, and MECP2/IRAK1. Results We found the first evidence of genetic association between lupus in African American patients and 5 susceptibility loci (C8orf13-BLK, BANK1, TNFSF4, KIAA1542, and CTLA4; P = 8.0 × 10-6, P = 1.9 × 10-5, P = 5.7 × 10-5, P = 0.00099, and P = 0.0045, respectively). Further, we confirmed the genetic association between lupus and 5 additional lupus susceptibility loci (ITGAM, MSH5, CFB, STAT4, and FCGR2A; P = 7.5 × 10-11, P = 5.2 × 10-8, P = 8.7 × 10 -7, P = 0.0058, and P = 0.0070, respectively), and provided evidence, for the first time, of genome-wide significance for the association between lupus in African American patients and ITGAM and MSH5 (HLA region). Conclusion These findings provide evidence of novel genetic susceptibility loci for lupus in African Americans and demonstrate that the majority of lupus susceptibility loci examined confer lupus risk across multiple ethnicities.

Original languageEnglish (US)
Pages (from-to)3493-3501
Number of pages9
JournalArthritis and Rheumatism
Volume63
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

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Genetic Loci
Genetic Association Studies
Genetic Predisposition to Disease
African Americans
Genome-Wide Association Study
Disease Susceptibility
Single Nucleotide Polymorphism
Genome
Genes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Sánchez, E., Comeau, M. E., Freedman, B. I., Kelly, J. A., Kaufman, K. M., Langefeld, C. D., ... Sawalha, A. H. (2011). Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study. Arthritis and Rheumatism, 63(11), 3493-3501. https://doi.org/10.1002/art.30563

Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study. / Sánchez, Elena; Comeau, Mary E.; Freedman, Barry I.; Kelly, Jennifer A.; Kaufman, Kenneth M.; Langefeld, Carl D.; Brown, Elizabeth E.; Alarcón, Graciela S.; Kimberly, Robert P.; Edberg, Jeffrey C.; Ramsey-Goldman, Rosalind; Petri, Michelle; Reveille, John D.; Vilá, Luis M.; Merrill, Joan T.; Tsao, Betty P.; Kamen, Diane L.; Gilkeson, Gary S.; James, Judith A.; Vyse, Timothy J.; Gaffney, Patrick M.; Jacob, Chaim O.; Niewold, Timothy B.; Richardson, Bruce C.; Harley, John B.; Alarcón-Riquelme, Marta E.; Sawalha, Amr H.

In: Arthritis and Rheumatism, Vol. 63, No. 11, 11.2011, p. 3493-3501.

Research output: Contribution to journalArticle

Sánchez, E, Comeau, ME, Freedman, BI, Kelly, JA, Kaufman, KM, Langefeld, CD, Brown, EE, Alarcón, GS, Kimberly, RP, Edberg, JC, Ramsey-Goldman, R, Petri, M, Reveille, JD, Vilá, LM, Merrill, JT, Tsao, BP, Kamen, DL, Gilkeson, GS, James, JA, Vyse, TJ, Gaffney, PM, Jacob, CO, Niewold, TB, Richardson, BC, Harley, JB, Alarcón-Riquelme, ME & Sawalha, AH 2011, 'Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study', Arthritis and Rheumatism, vol. 63, no. 11, pp. 3493-3501. https://doi.org/10.1002/art.30563
Sánchez, Elena ; Comeau, Mary E. ; Freedman, Barry I. ; Kelly, Jennifer A. ; Kaufman, Kenneth M. ; Langefeld, Carl D. ; Brown, Elizabeth E. ; Alarcón, Graciela S. ; Kimberly, Robert P. ; Edberg, Jeffrey C. ; Ramsey-Goldman, Rosalind ; Petri, Michelle ; Reveille, John D. ; Vilá, Luis M. ; Merrill, Joan T. ; Tsao, Betty P. ; Kamen, Diane L. ; Gilkeson, Gary S. ; James, Judith A. ; Vyse, Timothy J. ; Gaffney, Patrick M. ; Jacob, Chaim O. ; Niewold, Timothy B. ; Richardson, Bruce C. ; Harley, John B. ; Alarcón-Riquelme, Marta E. ; Sawalha, Amr H. / Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study. In: Arthritis and Rheumatism. 2011 ; Vol. 63, No. 11. pp. 3493-3501.
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title = "Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study",
abstract = "Objective Candidate gene and genome-wide association studies have identified several disease susceptibility loci in lupus patients. These studies have largely been performed in lupus patients who are Asian or of European ancestry. This study was undertaken to examine whether some of these same susceptibility loci increase lupus risk in African American individuals. Methods Single-nucleotide polymorphisms tagging 15 independent lupus susceptibility loci were genotyped in a set of 1,724 lupus patients and 2,024 healthy controls of African American descent. The loci examined included PTPN22, FCGR2A, TNFSF4, STAT4, CTLA4, PDCD1, PXK, BANK1, MSH5 (HLA region), CFB (HLA region), C8orf13-BLK region, MBL2, KIAA1542, ITGAM, and MECP2/IRAK1. Results We found the first evidence of genetic association between lupus in African American patients and 5 susceptibility loci (C8orf13-BLK, BANK1, TNFSF4, KIAA1542, and CTLA4; P = 8.0 × 10-6, P = 1.9 × 10-5, P = 5.7 × 10-5, P = 0.00099, and P = 0.0045, respectively). Further, we confirmed the genetic association between lupus and 5 additional lupus susceptibility loci (ITGAM, MSH5, CFB, STAT4, and FCGR2A; P = 7.5 × 10-11, P = 5.2 × 10-8, P = 8.7 × 10 -7, P = 0.0058, and P = 0.0070, respectively), and provided evidence, for the first time, of genome-wide significance for the association between lupus in African American patients and ITGAM and MSH5 (HLA region). Conclusion These findings provide evidence of novel genetic susceptibility loci for lupus in African Americans and demonstrate that the majority of lupus susceptibility loci examined confer lupus risk across multiple ethnicities.",
author = "Elena S{\'a}nchez and Comeau, {Mary E.} and Freedman, {Barry I.} and Kelly, {Jennifer A.} and Kaufman, {Kenneth M.} and Langefeld, {Carl D.} and Brown, {Elizabeth E.} and Alarc{\'o}n, {Graciela S.} and Kimberly, {Robert P.} and Edberg, {Jeffrey C.} and Rosalind Ramsey-Goldman and Michelle Petri and Reveille, {John D.} and Vil{\'a}, {Luis M.} and Merrill, {Joan T.} and Tsao, {Betty P.} and Kamen, {Diane L.} and Gilkeson, {Gary S.} and James, {Judith A.} and Vyse, {Timothy J.} and Gaffney, {Patrick M.} and Jacob, {Chaim O.} and Niewold, {Timothy B.} and Richardson, {Bruce C.} and Harley, {John B.} and Alarc{\'o}n-Riquelme, {Marta E.} and Sawalha, {Amr H.}",
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T1 - Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study

AU - Sánchez, Elena

AU - Comeau, Mary E.

AU - Freedman, Barry I.

AU - Kelly, Jennifer A.

AU - Kaufman, Kenneth M.

AU - Langefeld, Carl D.

AU - Brown, Elizabeth E.

AU - Alarcón, Graciela S.

AU - Kimberly, Robert P.

AU - Edberg, Jeffrey C.

AU - Ramsey-Goldman, Rosalind

AU - Petri, Michelle

AU - Reveille, John D.

AU - Vilá, Luis M.

AU - Merrill, Joan T.

AU - Tsao, Betty P.

AU - Kamen, Diane L.

AU - Gilkeson, Gary S.

AU - James, Judith A.

AU - Vyse, Timothy J.

AU - Gaffney, Patrick M.

AU - Jacob, Chaim O.

AU - Niewold, Timothy B.

AU - Richardson, Bruce C.

AU - Harley, John B.

AU - Alarcón-Riquelme, Marta E.

AU - Sawalha, Amr H.

PY - 2011/11

Y1 - 2011/11

N2 - Objective Candidate gene and genome-wide association studies have identified several disease susceptibility loci in lupus patients. These studies have largely been performed in lupus patients who are Asian or of European ancestry. This study was undertaken to examine whether some of these same susceptibility loci increase lupus risk in African American individuals. Methods Single-nucleotide polymorphisms tagging 15 independent lupus susceptibility loci were genotyped in a set of 1,724 lupus patients and 2,024 healthy controls of African American descent. The loci examined included PTPN22, FCGR2A, TNFSF4, STAT4, CTLA4, PDCD1, PXK, BANK1, MSH5 (HLA region), CFB (HLA region), C8orf13-BLK region, MBL2, KIAA1542, ITGAM, and MECP2/IRAK1. Results We found the first evidence of genetic association between lupus in African American patients and 5 susceptibility loci (C8orf13-BLK, BANK1, TNFSF4, KIAA1542, and CTLA4; P = 8.0 × 10-6, P = 1.9 × 10-5, P = 5.7 × 10-5, P = 0.00099, and P = 0.0045, respectively). Further, we confirmed the genetic association between lupus and 5 additional lupus susceptibility loci (ITGAM, MSH5, CFB, STAT4, and FCGR2A; P = 7.5 × 10-11, P = 5.2 × 10-8, P = 8.7 × 10 -7, P = 0.0058, and P = 0.0070, respectively), and provided evidence, for the first time, of genome-wide significance for the association between lupus in African American patients and ITGAM and MSH5 (HLA region). Conclusion These findings provide evidence of novel genetic susceptibility loci for lupus in African Americans and demonstrate that the majority of lupus susceptibility loci examined confer lupus risk across multiple ethnicities.

AB - Objective Candidate gene and genome-wide association studies have identified several disease susceptibility loci in lupus patients. These studies have largely been performed in lupus patients who are Asian or of European ancestry. This study was undertaken to examine whether some of these same susceptibility loci increase lupus risk in African American individuals. Methods Single-nucleotide polymorphisms tagging 15 independent lupus susceptibility loci were genotyped in a set of 1,724 lupus patients and 2,024 healthy controls of African American descent. The loci examined included PTPN22, FCGR2A, TNFSF4, STAT4, CTLA4, PDCD1, PXK, BANK1, MSH5 (HLA region), CFB (HLA region), C8orf13-BLK region, MBL2, KIAA1542, ITGAM, and MECP2/IRAK1. Results We found the first evidence of genetic association between lupus in African American patients and 5 susceptibility loci (C8orf13-BLK, BANK1, TNFSF4, KIAA1542, and CTLA4; P = 8.0 × 10-6, P = 1.9 × 10-5, P = 5.7 × 10-5, P = 0.00099, and P = 0.0045, respectively). Further, we confirmed the genetic association between lupus and 5 additional lupus susceptibility loci (ITGAM, MSH5, CFB, STAT4, and FCGR2A; P = 7.5 × 10-11, P = 5.2 × 10-8, P = 8.7 × 10 -7, P = 0.0058, and P = 0.0070, respectively), and provided evidence, for the first time, of genome-wide significance for the association between lupus in African American patients and ITGAM and MSH5 (HLA region). Conclusion These findings provide evidence of novel genetic susceptibility loci for lupus in African Americans and demonstrate that the majority of lupus susceptibility loci examined confer lupus risk across multiple ethnicities.

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