Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study

Christopher J. Lessard, Indra Adrianto, John A. Ice, Graham B. Wiley, Jennifer A. Kelly, Stuart B. Glenn, Adam J. Adler, He Li, Astrid Rasmussen, Adrienne H. Williams, Julie Ziegler, Mary E. Comeau, Miranda Marion, Benjamin E. Wakeland, Chaoying Liang, Paula S. Ramos, Kiely M. Grundahl, Caroline J. Gallant, Graciela S. Alarcón, Juan Manuel Anaya & 37 otros Sang Cheol Bae, Susan A. Boackle, Elizabeth E. Brown, Deh Ming Chang, Soo Kyung Cho, Lindsey A. Criswell, Jeffrey C. Edberg, Barry I. Freedman, Gary S. Gilkeson, Chaim O. Jacob, Judith A. James, Diane L. Kamen, Robert P. Kimberly, Jae Hoon Kim, Javier Martin, Joan T. Merrill, Timothy B. Niewold, So Yeon Park, Michelle A. Petri, Bernardo A. Pons-Estel, Rosalind Ramsey-Goldman, John D. Reveille, R. Hal Scofield, Yeong Wook Song, Anne M. Stevens, Betty P. Tsao, Luis M. Vila, Timothy J. Vyse, Chack Yung Yu, Joel M. Guthridge, Kenneth M. Kaufman, John B. Harley, Edward K. Wakeland, Carl D. Langefeld, Patrick M. Gaffney, Courtney G. Montgomery, Kathy L. Moser

Resultado de la investigación: Contribución a RevistaArtículo

101 Citas (Scopus)

Resumen

Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p meta-Euro = 2.08 × 10 -10), transmembrane protein 39A (TMEM39A; rs1132200; p meta-all = 8.62 × 10 -9), and 17q21 (rs1453560; p meta-all = 3.48 × 10 -10) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 × 10 -8 <p meta-Euro <9.99 × 10 -5) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4, FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation. © 2012 The American Society of Human Genetics.
Idioma originalEnglish (US)
Páginas (desde-hasta)648-660
Número de páginas13
PublicaciónAmerican Journal of Human Genetics
DOI
EstadoPublished - abr 6 2012

Huella dactilar

Zona Pellucida
Systemic Lupus Erythematosus
Carrier Proteins
Genome-Wide Association Study
Disease Susceptibility
Zinc Fingers
Autoantigens
Hispanic Americans
African Americans
Haplotypes
Interferons
Genes
Genome
Population
Proteins

Citar esto

Lessard, Christopher J. ; Adrianto, Indra ; Ice, John A. ; Wiley, Graham B. ; Kelly, Jennifer A. ; Glenn, Stuart B. ; Adler, Adam J. ; Li, He ; Rasmussen, Astrid ; Williams, Adrienne H. ; Ziegler, Julie ; Comeau, Mary E. ; Marion, Miranda ; Wakeland, Benjamin E. ; Liang, Chaoying ; Ramos, Paula S. ; Grundahl, Kiely M. ; Gallant, Caroline J. ; Alarcón, Graciela S. ; Anaya, Juan Manuel ; Bae, Sang Cheol ; Boackle, Susan A. ; Brown, Elizabeth E. ; Chang, Deh Ming ; Cho, Soo Kyung ; Criswell, Lindsey A. ; Edberg, Jeffrey C. ; Freedman, Barry I. ; Gilkeson, Gary S. ; Jacob, Chaim O. ; James, Judith A. ; Kamen, Diane L. ; Kimberly, Robert P. ; Kim, Jae Hoon ; Martin, Javier ; Merrill, Joan T. ; Niewold, Timothy B. ; Park, So Yeon ; Petri, Michelle A. ; Pons-Estel, Bernardo A. ; Ramsey-Goldman, Rosalind ; Reveille, John D. ; Scofield, R. Hal ; Song, Yeong Wook ; Stevens, Anne M. ; Tsao, Betty P. ; Vila, Luis M. ; Vyse, Timothy J. ; Yu, Chack Yung ; Guthridge, Joel M. ; Kaufman, Kenneth M. ; Harley, John B. ; Wakeland, Edward K. ; Langefeld, Carl D. ; Gaffney, Patrick M. ; Montgomery, Courtney G. ; Moser, Kathy L. / Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study. En: American Journal of Human Genetics. 2012 ; pp. 648-660.
@article{20eff164a7574991a68c593b71f602f3,
title = "Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study",
abstract = "Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p meta-Euro = 2.08 × 10 -10), transmembrane protein 39A (TMEM39A; rs1132200; p meta-all = 8.62 × 10 -9), and 17q21 (rs1453560; p meta-all = 3.48 × 10 -10) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 × 10 -8 <p meta-Euro <9.99 × 10 -5) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4, FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation. {\circledC} 2012 The American Society of Human Genetics.",
author = "Lessard, {Christopher J.} and Indra Adrianto and Ice, {John A.} and Wiley, {Graham B.} and Kelly, {Jennifer A.} and Glenn, {Stuart B.} and Adler, {Adam J.} and He Li and Astrid Rasmussen and Williams, {Adrienne H.} and Julie Ziegler and Comeau, {Mary E.} and Miranda Marion and Wakeland, {Benjamin E.} and Chaoying Liang and Ramos, {Paula S.} and Grundahl, {Kiely M.} and Gallant, {Caroline J.} and Alarc{\'o}n, {Graciela S.} and Anaya, {Juan Manuel} and Bae, {Sang Cheol} and Boackle, {Susan A.} and Brown, {Elizabeth E.} and Chang, {Deh Ming} and Cho, {Soo Kyung} and Criswell, {Lindsey A.} and Edberg, {Jeffrey C.} and Freedman, {Barry I.} and Gilkeson, {Gary S.} and Jacob, {Chaim O.} and James, {Judith A.} and Kamen, {Diane L.} and Kimberly, {Robert P.} and Kim, {Jae Hoon} and Javier Martin and Merrill, {Joan T.} and Niewold, {Timothy B.} and Park, {So Yeon} and Petri, {Michelle A.} and Pons-Estel, {Bernardo A.} and Rosalind Ramsey-Goldman and Reveille, {John D.} and Scofield, {R. Hal} and Song, {Yeong Wook} and Stevens, {Anne M.} and Tsao, {Betty P.} and Vila, {Luis M.} and Vyse, {Timothy J.} and Yu, {Chack Yung} and Guthridge, {Joel M.} and Kaufman, {Kenneth M.} and Harley, {John B.} and Wakeland, {Edward K.} and Langefeld, {Carl D.} and Gaffney, {Patrick M.} and Montgomery, {Courtney G.} and Moser, {Kathy L.}",
year = "2012",
month = "4",
day = "6",
doi = "10.1016/j.ajhg.2012.02.023",
language = "English (US)",
pages = "648--660",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",

}

Lessard, CJ, Adrianto, I, Ice, JA, Wiley, GB, Kelly, JA, Glenn, SB, Adler, AJ, Li, H, Rasmussen, A, Williams, AH, Ziegler, J, Comeau, ME, Marion, M, Wakeland, BE, Liang, C, Ramos, PS, Grundahl, KM, Gallant, CJ, Alarcón, GS, Anaya, JM, Bae, SC, Boackle, SA, Brown, EE, Chang, DM, Cho, SK, Criswell, LA, Edberg, JC, Freedman, BI, Gilkeson, GS, Jacob, CO, James, JA, Kamen, DL, Kimberly, RP, Kim, JH, Martin, J, Merrill, JT, Niewold, TB, Park, SY, Petri, MA, Pons-Estel, BA, Ramsey-Goldman, R, Reveille, JD, Scofield, RH, Song, YW, Stevens, AM, Tsao, BP, Vila, LM, Vyse, TJ, Yu, CY, Guthridge, JM, Kaufman, KM, Harley, JB, Wakeland, EK, Langefeld, CD, Gaffney, PM, Montgomery, CG & Moser, KL 2012, 'Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study', American Journal of Human Genetics, pp. 648-660. https://doi.org/10.1016/j.ajhg.2012.02.023

Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study. / Lessard, Christopher J.; Adrianto, Indra; Ice, John A.; Wiley, Graham B.; Kelly, Jennifer A.; Glenn, Stuart B.; Adler, Adam J.; Li, He; Rasmussen, Astrid; Williams, Adrienne H.; Ziegler, Julie; Comeau, Mary E.; Marion, Miranda; Wakeland, Benjamin E.; Liang, Chaoying; Ramos, Paula S.; Grundahl, Kiely M.; Gallant, Caroline J.; Alarcón, Graciela S.; Anaya, Juan Manuel; Bae, Sang Cheol; Boackle, Susan A.; Brown, Elizabeth E.; Chang, Deh Ming; Cho, Soo Kyung; Criswell, Lindsey A.; Edberg, Jeffrey C.; Freedman, Barry I.; Gilkeson, Gary S.; Jacob, Chaim O.; James, Judith A.; Kamen, Diane L.; Kimberly, Robert P.; Kim, Jae Hoon; Martin, Javier; Merrill, Joan T.; Niewold, Timothy B.; Park, So Yeon; Petri, Michelle A.; Pons-Estel, Bernardo A.; Ramsey-Goldman, Rosalind; Reveille, John D.; Scofield, R. Hal; Song, Yeong Wook; Stevens, Anne M.; Tsao, Betty P.; Vila, Luis M.; Vyse, Timothy J.; Yu, Chack Yung; Guthridge, Joel M.; Kaufman, Kenneth M.; Harley, John B.; Wakeland, Edward K.; Langefeld, Carl D.; Gaffney, Patrick M.; Montgomery, Courtney G.; Moser, Kathy L.

En: American Journal of Human Genetics, 06.04.2012, p. 648-660.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study

AU - Lessard, Christopher J.

AU - Adrianto, Indra

AU - Ice, John A.

AU - Wiley, Graham B.

AU - Kelly, Jennifer A.

AU - Glenn, Stuart B.

AU - Adler, Adam J.

AU - Li, He

AU - Rasmussen, Astrid

AU - Williams, Adrienne H.

AU - Ziegler, Julie

AU - Comeau, Mary E.

AU - Marion, Miranda

AU - Wakeland, Benjamin E.

AU - Liang, Chaoying

AU - Ramos, Paula S.

AU - Grundahl, Kiely M.

AU - Gallant, Caroline J.

AU - Alarcón, Graciela S.

AU - Anaya, Juan Manuel

AU - Bae, Sang Cheol

AU - Boackle, Susan A.

AU - Brown, Elizabeth E.

AU - Chang, Deh Ming

AU - Cho, Soo Kyung

AU - Criswell, Lindsey A.

AU - Edberg, Jeffrey C.

AU - Freedman, Barry I.

AU - Gilkeson, Gary S.

AU - Jacob, Chaim O.

AU - James, Judith A.

AU - Kamen, Diane L.

AU - Kimberly, Robert P.

AU - Kim, Jae Hoon

AU - Martin, Javier

AU - Merrill, Joan T.

AU - Niewold, Timothy B.

AU - Park, So Yeon

AU - Petri, Michelle A.

AU - Pons-Estel, Bernardo A.

AU - Ramsey-Goldman, Rosalind

AU - Reveille, John D.

AU - Scofield, R. Hal

AU - Song, Yeong Wook

AU - Stevens, Anne M.

AU - Tsao, Betty P.

AU - Vila, Luis M.

AU - Vyse, Timothy J.

AU - Yu, Chack Yung

AU - Guthridge, Joel M.

AU - Kaufman, Kenneth M.

AU - Harley, John B.

AU - Wakeland, Edward K.

AU - Langefeld, Carl D.

AU - Gaffney, Patrick M.

AU - Montgomery, Courtney G.

AU - Moser, Kathy L.

PY - 2012/4/6

Y1 - 2012/4/6

N2 - Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p meta-Euro = 2.08 × 10 -10), transmembrane protein 39A (TMEM39A; rs1132200; p meta-all = 8.62 × 10 -9), and 17q21 (rs1453560; p meta-all = 3.48 × 10 -10) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 × 10 -8 <p meta-Euro <9.99 × 10 -5) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4, FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation. © 2012 The American Society of Human Genetics.

AB - Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p meta-Euro = 2.08 × 10 -10), transmembrane protein 39A (TMEM39A; rs1132200; p meta-all = 8.62 × 10 -9), and 17q21 (rs1453560; p meta-all = 3.48 × 10 -10) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 × 10 -8 <p meta-Euro <9.99 × 10 -5) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4, FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation. © 2012 The American Society of Human Genetics.

U2 - 10.1016/j.ajhg.2012.02.023

DO - 10.1016/j.ajhg.2012.02.023

M3 - Article

SP - 648

EP - 660

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

ER -