Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

Maureen D. Mayes, Lara Bossini-Castillo, Olga Gorlova, José Ezequiel Martin, Xiaodong Zhou, Wei V. Chen, Shervin Assassi, Jun Ying, Filemon K. Tan, Frank C. Arnett, John D. Reveille, Sandra Guerra, María Teruel, Francisco David Carmona, Peter K. Gregersen, Annette T. Lee, Elena López-Isac, Eguzkine Ochoa, Patricia Carreira, Carmen Pilar SimeónIván Castellví, Miguel Ángel González-Gay, Alexandra Zhernakova, Leonid Padyukov, Marta Alarcón-Riquelme, Cisca Wijmenga, Matthew Brown, Lorenzo Beretta, Gabriela Riemekasten, Torsten Witte, Nicolas Hunzelmann, Alexander Kreuter, Jörg H W Distler, Alexandre E. Voskuyl, Annemie J. Schuerwegh, Roger Hesselstrand, Annika Nordin, Paolo Airó, Claudio Lunardi, Paul Shiels, Jacob M. Van Laar, Ariane Herrick, Jane Worthington, Christopher Denton, Fredrick M. Wigley, Laura K. Hummers, John Varga, Monique E. Hinchcliff, Murray Baron, Marie Hudson, Janet E. Pope, Daniel E. Furst, Dinesh Khanna, Kristin Phillips, Elena Schiopu, Barbara M. Segal, Jerry A. Molitor, Richard M. Silver, Virginia D. Steen, Robert W. Simms, Robert A. Lafyatis, Barri J. Fessler, Tracy M. Frech, Firas Alkassab, Peter Docherty, Elzbieta Kaminska, Nader Khalidi, Henry Niall Jones, Janet Markland, David Robinson, Jasper Broen, Timothy R D J Radstake, Carmen Fonseca, Bobby P. Koeleman, Javier Martin

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.

Original languageEnglish
Pages (from-to)47-61
Number of pages15
JournalAmerican Journal of Human Genetics
Volume94
Issue number1
DOIs
Publication statusPublished - Jan 2 2014

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Systemic Scleroderma
HLA Antigens
Single Nucleotide Polymorphism
Amino Acids
Alleles

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Mayes, M. D., Bossini-Castillo, L., Gorlova, O., Martin, J. E., Zhou, X., Chen, W. V., ... Martin, J. (2014). Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis. American Journal of Human Genetics, 94(1), 47-61. https://doi.org/10.1016/j.ajhg.2013.12.002

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis. / Mayes, Maureen D.; Bossini-Castillo, Lara; Gorlova, Olga; Martin, José Ezequiel; Zhou, Xiaodong; Chen, Wei V.; Assassi, Shervin; Ying, Jun; Tan, Filemon K.; Arnett, Frank C.; Reveille, John D.; Guerra, Sandra; Teruel, María; Carmona, Francisco David; Gregersen, Peter K.; Lee, Annette T.; López-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeón, Carmen Pilar; Castellví, Iván; González-Gay, Miguel Ángel; Zhernakova, Alexandra; Padyukov, Leonid; Alarcón-Riquelme, Marta; Wijmenga, Cisca; Brown, Matthew; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg H W; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Hesselstrand, Roger; Nordin, Annika; Airó, Paolo; Lunardi, Claudio; Shiels, Paul; Van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M.; Hummers, Laura K.; Varga, John; Hinchcliff, Monique E.; Baron, Murray; Hudson, Marie; Pope, Janet E.; Furst, Daniel E.; Khanna, Dinesh; Phillips, Kristin; Schiopu, Elena; Segal, Barbara M.; Molitor, Jerry A.; Silver, Richard M.; Steen, Virginia D.; Simms, Robert W.; Lafyatis, Robert A.; Fessler, Barri J.; Frech, Tracy M.; Alkassab, Firas; Docherty, Peter; Kaminska, Elzbieta; Khalidi, Nader; Jones, Henry Niall; Markland, Janet; Robinson, David; Broen, Jasper; Radstake, Timothy R D J; Fonseca, Carmen; Koeleman, Bobby P.; Martin, Javier.

In: American Journal of Human Genetics, Vol. 94, No. 1, 02.01.2014, p. 47-61.

Research output: Contribution to journalArticle

Mayes, MD, Bossini-Castillo, L, Gorlova, O, Martin, JE, Zhou, X, Chen, WV, Assassi, S, Ying, J, Tan, FK, Arnett, FC, Reveille, JD, Guerra, S, Teruel, M, Carmona, FD, Gregersen, PK, Lee, AT, López-Isac, E, Ochoa, E, Carreira, P, Simeón, CP, Castellví, I, González-Gay, MÁ, Zhernakova, A, Padyukov, L, Alarcón-Riquelme, M, Wijmenga, C, Brown, M, Beretta, L, Riemekasten, G, Witte, T, Hunzelmann, N, Kreuter, A, Distler, JHW, Voskuyl, AE, Schuerwegh, AJ, Hesselstrand, R, Nordin, A, Airó, P, Lunardi, C, Shiels, P, Van Laar, JM, Herrick, A, Worthington, J, Denton, C, Wigley, FM, Hummers, LK, Varga, J, Hinchcliff, ME, Baron, M, Hudson, M, Pope, JE, Furst, DE, Khanna, D, Phillips, K, Schiopu, E, Segal, BM, Molitor, JA, Silver, RM, Steen, VD, Simms, RW, Lafyatis, RA, Fessler, BJ, Frech, TM, Alkassab, F, Docherty, P, Kaminska, E, Khalidi, N, Jones, HN, Markland, J, Robinson, D, Broen, J, Radstake, TRDJ, Fonseca, C, Koeleman, BP & Martin, J 2014, 'Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis', American Journal of Human Genetics, vol. 94, no. 1, pp. 47-61. https://doi.org/10.1016/j.ajhg.2013.12.002
Mayes, Maureen D. ; Bossini-Castillo, Lara ; Gorlova, Olga ; Martin, José Ezequiel ; Zhou, Xiaodong ; Chen, Wei V. ; Assassi, Shervin ; Ying, Jun ; Tan, Filemon K. ; Arnett, Frank C. ; Reveille, John D. ; Guerra, Sandra ; Teruel, María ; Carmona, Francisco David ; Gregersen, Peter K. ; Lee, Annette T. ; López-Isac, Elena ; Ochoa, Eguzkine ; Carreira, Patricia ; Simeón, Carmen Pilar ; Castellví, Iván ; González-Gay, Miguel Ángel ; Zhernakova, Alexandra ; Padyukov, Leonid ; Alarcón-Riquelme, Marta ; Wijmenga, Cisca ; Brown, Matthew ; Beretta, Lorenzo ; Riemekasten, Gabriela ; Witte, Torsten ; Hunzelmann, Nicolas ; Kreuter, Alexander ; Distler, Jörg H W ; Voskuyl, Alexandre E. ; Schuerwegh, Annemie J. ; Hesselstrand, Roger ; Nordin, Annika ; Airó, Paolo ; Lunardi, Claudio ; Shiels, Paul ; Van Laar, Jacob M. ; Herrick, Ariane ; Worthington, Jane ; Denton, Christopher ; Wigley, Fredrick M. ; Hummers, Laura K. ; Varga, John ; Hinchcliff, Monique E. ; Baron, Murray ; Hudson, Marie ; Pope, Janet E. ; Furst, Daniel E. ; Khanna, Dinesh ; Phillips, Kristin ; Schiopu, Elena ; Segal, Barbara M. ; Molitor, Jerry A. ; Silver, Richard M. ; Steen, Virginia D. ; Simms, Robert W. ; Lafyatis, Robert A. ; Fessler, Barri J. ; Frech, Tracy M. ; Alkassab, Firas ; Docherty, Peter ; Kaminska, Elzbieta ; Khalidi, Nader ; Jones, Henry Niall ; Markland, Janet ; Robinson, David ; Broen, Jasper ; Radstake, Timothy R D J ; Fonseca, Carmen ; Koeleman, Bobby P. ; Martin, Javier. / Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis. In: American Journal of Human Genetics. 2014 ; Vol. 94, No. 1. pp. 47-61.
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AU - Mayes, Maureen D.

AU - Bossini-Castillo, Lara

AU - Gorlova, Olga

AU - Martin, José Ezequiel

AU - Zhou, Xiaodong

AU - Chen, Wei V.

AU - Assassi, Shervin

AU - Ying, Jun

AU - Tan, Filemon K.

AU - Arnett, Frank C.

AU - Reveille, John D.

AU - Guerra, Sandra

AU - Teruel, María

AU - Carmona, Francisco David

AU - Gregersen, Peter K.

AU - Lee, Annette T.

AU - López-Isac, Elena

AU - Ochoa, Eguzkine

AU - Carreira, Patricia

AU - Simeón, Carmen Pilar

AU - Castellví, Iván

AU - González-Gay, Miguel Ángel

AU - Zhernakova, Alexandra

AU - Padyukov, Leonid

AU - Alarcón-Riquelme, Marta

AU - Wijmenga, Cisca

AU - Brown, Matthew

AU - Beretta, Lorenzo

AU - Riemekasten, Gabriela

AU - Witte, Torsten

AU - Hunzelmann, Nicolas

AU - Kreuter, Alexander

AU - Distler, Jörg H W

AU - Voskuyl, Alexandre E.

AU - Schuerwegh, Annemie J.

AU - Hesselstrand, Roger

AU - Nordin, Annika

AU - Airó, Paolo

AU - Lunardi, Claudio

AU - Shiels, Paul

AU - Van Laar, Jacob M.

AU - Herrick, Ariane

AU - Worthington, Jane

AU - Denton, Christopher

AU - Wigley, Fredrick M.

AU - Hummers, Laura K.

AU - Varga, John

AU - Hinchcliff, Monique E.

AU - Baron, Murray

AU - Hudson, Marie

AU - Pope, Janet E.

AU - Furst, Daniel E.

AU - Khanna, Dinesh

AU - Phillips, Kristin

AU - Schiopu, Elena

AU - Segal, Barbara M.

AU - Molitor, Jerry A.

AU - Silver, Richard M.

AU - Steen, Virginia D.

AU - Simms, Robert W.

AU - Lafyatis, Robert A.

AU - Fessler, Barri J.

AU - Frech, Tracy M.

AU - Alkassab, Firas

AU - Docherty, Peter

AU - Kaminska, Elzbieta

AU - Khalidi, Nader

AU - Jones, Henry Niall

AU - Markland, Janet

AU - Robinson, David

AU - Broen, Jasper

AU - Radstake, Timothy R D J

AU - Fonseca, Carmen

AU - Koeleman, Bobby P.

AU - Martin, Javier

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