Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study

Christopher J. Lessard; Indra Adrianto; Jennifer A. Kelly; Kenneth M. Kaufman; Kiely M. Grundahl; Adam Adler; Adrienne H. Williams; Caroline J. Gallant; Juan Manuel Anaya; Sang Cheol Bae; Susan A. Boackle; Elizabeth E. Brown; Deh Ming Chang; Lindsey A. Criswell; Jeffrey C. Edberg; Barry I. Freedman; Peter K. Gregersen; Gary S. Gilkeson; Chaim O. Jacob; Judith A. James; Diane L. Kamen; Robert P. Kimberly; Javier Martin; Joan T. Merrill; Timothy B. Niewold; So Yeon Park; Michelle A. Petri; Bernardo A. Pons-Estel; Rosalind Ramsey-Goldman; John D. Reveille; Yeong Wook Song; Anne M. Stevens; Betty P. Tsao; Luis M. Vila; Timothy J. Vyse; Chack Yung Yu; Joel M. Guthridge; Gail R. Bruner; Carl D. Langefeld; Courtney Montgomery; John B. Harley; R. Hal Scofield; Patrick M. Gaffney; Kathy L. Moser

doi:10.1016/j.ajhg.2010.11.014

Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study

Christopher J. Lessard, Indra Adrianto, Jennifer A. Kelly, Kenneth M. Kaufman, Kiely M. Grundahl, Adam Adler, Adrienne H. Williams, Caroline J. Gallant, Juan Manuel Anaya, Sang Cheol Bae, Susan A. Boackle, Elizabeth E. Brown, Deh Ming Chang, Lindsey A. Criswell, Jeffrey C. Edberg, Barry I. Freedman, Peter K. Gregersen, Gary S. Gilkeson, Chaim O. Jacob, Judith A. JamesDiane L. Kamen, Robert P. Kimberly, Javier Martin, Joan T. Merrill, Timothy B. Niewold, So Yeon Park, Michelle A. Petri, Bernardo A. Pons-Estel, Rosalind Ramsey-Goldman, John D. Reveille, Yeong Wook Song, Anne M. Stevens, Betty P. Tsao, Luis M. Vila, Timothy J. Vyse, Chack Yung Yu, Joel M. Guthridge, Gail R. Bruner, Carl D. Langefeld, Courtney Montgomery, John B. Harley, R. Hal Scofield, Patrick M. Gaffney, Kathy L. Moser

Rheumatology

Research output: Contribution to journal › Article › peer-review

71 Scopus citations

Abstract

Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 × 10^-8) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 × 10^-8, OR = 0.83) and rs387619 (p = 7.7 × 10^-7, OR = 0.83) in the European samples with p_meta = 1.82 × 10^-9 for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 × 10^-3, OR = 0.81 and p = 4.3 × 10^-4, OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced p_meta = 2.36 × 10^-13. This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.

Original language	English (US)
Pages (from-to)	83-91
Number of pages	9
Journal	American journal of human genetics
Volume	88
Issue number	1
DOIs	https://doi.org/10.1016/j.ajhg.2010.11.014
State	Published - Jan 7 2011

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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Lessard, C. J., Adrianto, I., Kelly, J. A., Kaufman, K. M., Grundahl, K. M., Adler, A., Williams, A. H., Gallant, C. J., Anaya, J. M., Bae, S. C., Boackle, S. A., Brown, E. E., Chang, D. M., Criswell, L. A., Edberg, J. C., Freedman, B. I., Gregersen, P. K., Gilkeson, G. S., Jacob, C. O., ... Moser, K. L. (2011). Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study. American journal of human genetics, 88(1), 83-91. https://doi.org/10.1016/j.ajhg.2010.11.014

Lessard, CJ, Adrianto, I, Kelly, JA, Kaufman, KM, Grundahl, KM, Adler, A, Williams, AH, Gallant, CJ, Anaya, JM, Bae, SC, Boackle, SA, Brown, EE, Chang, DM, Criswell, LA, Edberg, JC, Freedman, BI, Gregersen, PK, Gilkeson, GS, Jacob, CO, James, JA, Kamen, DL, Kimberly, RP, Martin, J, Merrill, JT, Niewold, TB, Park, SY, Petri, MA, Pons-Estel, BA, Ramsey-Goldman, R, Reveille, JD, Song, YW, Stevens, AM, Tsao, BP, Vila, LM, Vyse, TJ, Yu, CY, Guthridge, JM, Bruner, GR, Langefeld, CD, Montgomery, C, Harley, JB, Scofield, RH, Gaffney, PM & Moser, KL 2011, 'Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study', American journal of human genetics, vol. 88, no. 1, pp. 83-91. https://doi.org/10.1016/j.ajhg.2010.11.014

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title = "Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study",

abstract = "Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 × 10-8) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 × 10-8, OR = 0.83) and rs387619 (p = 7.7 × 10-7, OR = 0.83) in the European samples with pmeta = 1.82 × 10-9 for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 × 10-3, OR = 0.81 and p = 4.3 × 10-4, OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced pmeta = 2.36 × 10-13. This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.",

author = "Lessard, {Christopher J.} and Indra Adrianto and Kelly, {Jennifer A.} and Kaufman, {Kenneth M.} and Grundahl, {Kiely M.} and Adam Adler and Williams, {Adrienne H.} and Gallant, {Caroline J.} and Anaya, {Juan Manuel} and Bae, {Sang Cheol} and Boackle, {Susan A.} and Brown, {Elizabeth E.} and Chang, {Deh Ming} and Criswell, {Lindsey A.} and Edberg, {Jeffrey C.} and Freedman, {Barry I.} and Gregersen, {Peter K.} and Gilkeson, {Gary S.} and Jacob, {Chaim O.} and James, {Judith A.} and Kamen, {Diane L.} and Kimberly, {Robert P.} 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 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 Bruner, {Gail R.} and Langefeld, {Carl D.} and Courtney Montgomery and Harley, {John B.} and Scofield, {R. Hal} and Gaffney, {Patrick M.} and Moser, {Kathy L.}",

year = "2011",

month = jan,

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doi = "10.1016/j.ajhg.2010.11.014",

language = "English (US)",

volume = "88",

pages = "83--91",

journal = "American journal of human genetics",

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T1 - Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study

AU - Lessard, Christopher J.

AU - Adrianto, Indra

AU - Kelly, Jennifer A.

AU - Kaufman, Kenneth M.

AU - Grundahl, Kiely M.

AU - Adler, Adam

AU - Williams, Adrienne H.

AU - Gallant, Caroline J.

AU - Anaya, Juan Manuel

AU - Bae, Sang Cheol

AU - Boackle, Susan A.

AU - Brown, Elizabeth E.

AU - Chang, Deh Ming

AU - Criswell, Lindsey A.

AU - Edberg, Jeffrey C.

AU - Freedman, Barry I.

AU - Gregersen, Peter K.

AU - Gilkeson, Gary S.

AU - Jacob, Chaim O.

AU - James, Judith A.

AU - Kamen, Diane L.

AU - Kimberly, Robert P.

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 - 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 - Bruner, Gail R.

AU - Langefeld, Carl D.

AU - Montgomery, Courtney

AU - Harley, John B.

AU - Scofield, R. Hal

AU - Gaffney, Patrick M.

AU - Moser, Kathy L.

PY - 2011/1/7

Y1 - 2011/1/7

N2 - Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 × 10-8) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 × 10-8, OR = 0.83) and rs387619 (p = 7.7 × 10-7, OR = 0.83) in the European samples with pmeta = 1.82 × 10-9 for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 × 10-3, OR = 0.81 and p = 4.3 × 10-4, OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced pmeta = 2.36 × 10-13. This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.

AB - Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 × 10-8) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 × 10-8, OR = 0.83) and rs387619 (p = 7.7 × 10-7, OR = 0.83) in the European samples with pmeta = 1.82 × 10-9 for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 × 10-3, OR = 0.81 and p = 4.3 × 10-4, OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced pmeta = 2.36 × 10-13. This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.

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Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study

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