Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis
Por:
Mayes, MD, Bossini-Castillo, L, Gorlova, O, Martin, JE, Zhou, XD, Chen, WV, Assassi, S, Ying, J, Tan, FK, Arnett, FC, Reveille, JD, Guerra, S, Terue, M, Carmona, FD, Gregersen, PK, Lee, AT, Lopez-Isac, E, Ochoa, E, Carreira, P, Simeon, CP, Castellvi, I, Gonzalez-Gay, MA, Zhernakova, A, Padyukov, L, Aarcon-Riquelme, M, Wijmenga, C, Brown, M, Beretta, L, Riemekasten, G, Witte, T, Hunzelmann, N, Kreuter, A, Distler, JHW, Voskuy, AE, Schuerwegh, AJ, Hesselstrand, R, Nordin, A, Airo, 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, BIJ, 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
Publicada:
2 ene 2014
Resumen:
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.
Filiaciones:
Mayes, MD:
Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA
Bossini-Castillo, L:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain
Gorlova, O:
Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA
Martin, JE:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain
Zhou, XD:
Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA
Chen, WV:
Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA
Assassi, S:
Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA
Ying, J:
Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA
Tan, FK:
Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA
Arnett, FC:
Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA
Reveille, JD:
Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA
Guerra, S:
UCL, Sch Med, Ctr Rheumatol, London WC1E 6BT, England
Terue, M:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain
Carmona, FD:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain
Gregersen, PK:
North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA
Lee, AT:
North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA
Lopez-Isac, E:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain
Ochoa, E:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain
Carreira, P:
Hosp Univ 12 Octubre, Dept Rheumatol, Madrid 28041, Spain
Simeon, CP:
Hosp Valle De Hebron, Dept Internal Med, Barcelona 08035, Spain
Castellvi, I:
Hosp Santa Creu & Sant Pau, Dept Rheumatol, Barcelona 08025, Spain
Gonzalez-Gay, MA:
Hosp Univ Marques de Valdecilla, Inst Formac Invest Marques de Valdecilla, Dept Rheumatol, Santander 39008, Spain
Zhernakova, A:
Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 Groningen, Netherlands
Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden
Padyukov, L:
Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden
Aarcon-Riquelme, M:
Univ Granada, Ctr Pfizer, Area Variabilidad ADN Humano, Junta Andalucia Genom & Invest Oncol, Granada 18016, Spain
Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA
Wijmenga, C:
Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 Groningen, Netherlands
Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden
Brown, M:
Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4072, Australia
Beretta, L:
Fdn IRCCS Ca Granda Osped Maggiore Policlin Milan, Referral Ctr Syst Autoimmune Dis, I-20122 Milan, Italy
Riemekasten, G:
Charite, Dept Rheumatol & Clin Immunol, D-10117 Berlin, Germany
Witte, T:
Hannover Med Sch, Dept Clin Immunol, D-30625 Hannover, Germany
Hunzelmann, N:
Univ Cologne, Dept Dermatol, D-50924 Cologne, Germany
Kreuter, A:
HELIOS St Elisabeth Hosp, Dept Dermatol Venereol & Allergol, D-46045 Oberhausen, Germany
Distler, JHW:
Univ Erlangen Nurnberg, Inst Clin Immunol, Dept Internal Med, D-91054 Erlangen, Germany
Voskuy, AE:
Vrije Univ Amsterdam, Med Ctr, Dept Rheumatol, NL-1081 HV Amsterdam, Netherlands
Schuerwegh, AJ:
Leiden Univ, Med Ctr, Dept Rheumatol & Pathol, NL-2300 RC Leiden, Netherlands
Leiden Univ, Med Ctr, Cent Med Immunol Lab, NL-2300 RC Leiden, Netherlands
Hesselstrand, R:
Lund Univ, Dept Rheumatol, S-22185 Lund, Sweden
Nordin, A:
Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden
Airo, P:
Spedali Civil Brescia, Serv Reumatol & Immunol Clin, I-25123 Brescia, Italy
Lunardi, C:
Univ Verona, Dept Med, I-37134 Verona, Italy
Shiels, P:
Univ Glasgow, Glasgow Biomed Res Ctr, Glasgow G61 1BD, Lanark, Scotland
van Laar, JM:
Newcastle Univ, Inst Cellular Med, Musculoskeletal Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
Herrick, A:
Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester M13 9PT, Lancs, England
Worthington, J:
Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester M13 9PT, Lancs, England
Denton, C:
UCL, Sch Med, Ctr Rheumatol, London WC1E 6BT, England
Wigley, FM:
Johns Hopkins Univ, Div Rheumatol, Baltimore, MD 21224 USA
Hummers, LK:
Johns Hopkins Univ, Div Rheumatol, Baltimore, MD 21224 USA
Varga, J:
Northwestern Univ, Div Rheumatol, Chicago, IL 60611 USA
Hinchcliff, ME:
Northwestern Univ, Div Rheumatol, Chicago, IL 60611 USA
Baron, M:
McGill Univ, Jewish Gen Hosp, Dept Rheumatol, Montreal, PQ H3T 1E2, Canada
Hudson, M:
McGill Univ, Jewish Gen Hosp, Dept Rheumatol, Montreal, PQ H3T 1E2, Canada
Pope, JE:
Univ Western Ontario, Div Rheumatol, London, ON N6A 4V2, Canada
Furst, DE:
Univ Calif Los Angeles, Div Rheumatol, Los Angeles, CA 90095 USA
Khanna, D:
Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA
Phillips, K:
Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA
Schiopu, E:
Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA
Segal, BM:
Univ Minnesota, Div Rheumatol, Minneapolis, MN 55455 USA
Molitor, JA:
Univ Minnesota, Div Rheumat & Autoimmune Dis, Minneapolis, MN 55455 USA
Silver, RM:
Med Univ S Carolina, Div Rheumatol, Charleston, SC 29425 USA
Steen, VD:
Georgetown Univ, Med Ctr, Div Rheumatol, Washington, DC 20007 USA
Simms, RW:
Boston Univ, Div Rheumatol, Boston, MA 02118 USA
Lafyatis, RA:
Boston Univ, Div Rheumatol, Boston, MA 02118 USA
Fessler, BIJ:
Univ Alabama Birmingham, Div Rheumatol, Birmingham, AL 35294 USA
Frech, TM:
Univ Utah, Div Rheumatol, Salt Lake City, UT 84132 USA
AlKassab, F:
Carolinas Healthcare Syst, Dept Rheumatol, Charlotte, NC 28211 USA
Docherty, P:
Moncton Hosp, Dept Rheumatol, Moncton, NB E1C 6Z8, Canada
Kaminska, E:
Alberta Hlth Serv, Dept Med, Rheumatol Sect, Calgary, AB T2N 2T9, Canada
Khalidi, N:
McMaster Univ, Dept Med, Div Rheumatol, Hamilton, ON L8N 1Y2, Canada
Jones, HN:
Univ Edmonton, Dept Rheumatol, Edmonton, AB T5M 0H4, Canada
Markland, J:
Univ Saskatchewan, Dept Rheumatol, Saskatoon, SK S7K 0H6, Canada
Robinson, D:
Univ Manitoba, Dept Rheumatol, Arthrit Ctr, Winnipeg, MB R3A 1M4, Canada
Broen, J:
Radboud Univ Nijmegen, Dept Rheumatol, Med Ctr, NL-6500 HC Nijmegen, Netherlands
Univ Med Ctr Utrecht, Dept Rheumatol & Clin Immunol, NL-3584 CX Utrecht, Netherlands
Radstake, TRDJ:
Radboud Univ Nijmegen, Dept Rheumatol, Med Ctr, NL-6500 HC Nijmegen, Netherlands
Univ Med Ctr Utrecht, Dept Rheumatol & Clin Immunol, NL-3584 CX Utrecht, Netherlands
Fonseca, C:
UCL, Sch Med, Ctr Rheumatol, London WC1E 6BT, England
Koeleman, BP:
Univ Med Ctr Utrecht, Dept Med Genet, Complex Genet Sect, NL-3584 CX Utrecht, Netherlands
Martin, J:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain
Green Published, Bronze, Green Accepted
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