OBJECTIVE: Genome-wide association studies (GWAS) in individuals of European ancestry identified a number of systemic lupus erythematosus (SLE) susceptibility loci using earlier versions of high-density genotyping platforms. Followup studies on suggestive GWAS regions using larger samples and more markers identified additional SLE loci in subjects of European descent. This multistage study was undertaken to identify novel SLE loci. METHODS: In stage 1, we conducted a new GWAS of SLE in a North American case-control sample of subjects of European ancestry (n = 1,166) genotyped on Affymetrix Genome-Wide Human SNP Array 6.0. In stage 2, we further investigated top new suggestive GWAS hits by in silico evaluation and meta-analysis using an additional data set of subjects of European descent (>2,500 individuals), followed by replication of top meta-analysis findings in another data set of subjects of European descent (>10,000 individuals) in stage 3. RESULTS: As expected, our GWAS revealed the most significant associations at the major histocompatibility complex locus (6p21), which easily surpassed the genome-wide significance threshold (P < 5 × 10(-8)). Several other SLE signals/loci previously implicated in Caucasians and/or Asians were also confirmed in the stage 1 discovery sample, and the strongest signals were observed at 2q32/STAT4 (P = 3.6 × 10(-7)) and at 8p23/BLK (P = 8.1 × 10(-6)). Stage 2 meta-analyses identified a new genome-wide significant SLE locus at 12q12 (meta P = 3.1 × 10(-8)), which was replicated in stage 3. CONCLUSION: Our multistage study identified and replicated a new SLE locus that warrants further followup in additional studies. Publicly available databases suggest that this newly identified SLE signal falls within a functionally relevant genomic region and near biologically important genes.
OBJECTIVE: Genome-wide association studies (GWAS) in individuals of European ancestry identified a number of systemic lupus erythematosus (SLE) susceptibility loci using earlier versions of high-density genotyping platforms. Followup studies on suggestive GWAS regions using larger samples and more markers identified additional SLE loci in subjects of European descent. This multistage study was undertaken to identify novel SLE loci. METHODS: In stage 1, we conducted a new GWAS of SLE in a North American case-control sample of subjects of European ancestry (n = 1,166) genotyped on Affymetrix Genome-Wide Human SNP Array 6.0. In stage 2, we further investigated top new suggestive GWAS hits by in silico evaluation and meta-analysis using an additional data set of subjects of European descent (>2,500 individuals), followed by replication of top meta-analysis findings in another data set of subjects of European descent (>10,000 individuals) in stage 3. RESULTS: As expected, our GWAS revealed the most significant associations at the major histocompatibility complex locus (6p21), which easily surpassed the genome-wide significance threshold (P < 5 × 10(-8)). Several other SLE signals/loci previously implicated in Caucasians and/or Asians were also confirmed in the stage 1 discovery sample, and the strongest signals were observed at 2q32/STAT4 (P = 3.6 × 10(-7)) and at 8p23/BLK (P = 8.1 × 10(-6)). Stage 2 meta-analyses identified a new genome-wide significant SLE locus at 12q12 (meta P = 3.1 × 10(-8)), which was replicated in stage 3. CONCLUSION: Our multistage study identified and replicated a new SLE locus that warrants further followup in additional studies. Publicly available databases suggest that this newly identified SLE signal falls within a functionally relevant genomic region and near biologically important genes.
Authors: Sasha Bernatsky; Rosalind Ramsey-Goldman; Jeremy Labrecque; Lawrence Joseph; Jean-Francois Boivin; Michelle Petri; Asad Zoma; Susan Manzi; Murray B Urowitz; Dafna Gladman; Paul R Fortin; Ellen Ginzler; Edward Yelin; Sang-Cheol Bae; Daniel J Wallace; Steven Edworthy; Soren Jacobsen; Caroline Gordon; Mary Anne Dooley; Christine A Peschken; John G Hanly; Graciela S Alarcón; Ola Nived; Guillermo Ruiz-Irastorza; David Isenberg; Anisur Rahman; Torsten Witte; Cynthia Aranow; Diane L Kamen; Kristjan Steinsson; Anca Askanase; Susan Barr; Lindsey A Criswell; Gunnar Sturfelt; Neha M Patel; Jean-Luc Senécal; Michel Zummer; Janet E Pope; Stephanie Ensworth; Hani El-Gabalawy; Timothy McCarthy; Lene Dreyer; John Sibley; Yvan St Pierre; Ann E Clarke Journal: J Autoimmun Date: 2013-02-12 Impact factor: 7.094
Authors: F Yesim K Demirci; Amy S Dressen; Candace M Kammerer; M Michael Barmada; Amy H Kao; Rosalind Ramsey-Goldman; Susan Manzi; M Ilyas Kamboh Journal: J Rheumatol Date: 2011-01-15 Impact factor: 4.666
Authors: Geoffrey Hom; Robert R Graham; Barmak Modrek; Kimberly E Taylor; Ward Ortmann; Sophie Garnier; Annette T Lee; Sharon A Chung; Ricardo C Ferreira; P V Krishna Pant; Dennis G Ballinger; Roman Kosoy; F Yesim Demirci; M Ilyas Kamboh; Amy H Kao; Chao Tian; Iva Gunnarsson; Anders A Bengtsson; Solbritt Rantapää-Dahlqvist; Michelle Petri; Susan Manzi; Michael F Seldin; Lars Rönnblom; Ann-Christine Syvänen; Lindsey A Criswell; Peter K Gregersen; Timothy W Behrens Journal: N Engl J Med Date: 2008-01-20 Impact factor: 91.245
Authors: Deborah S Cunninghame Graham; David L Morris; Tushar R Bhangale; Lindsey A Criswell; Ann-Christine Syvänen; Lars Rönnblom; Timothy W Behrens; Robert R Graham; Timothy J Vyse Journal: PLoS Genet Date: 2011-10-27 Impact factor: 5.917
Authors: Alexander G Bassuk; Robyn H Wallace; Aimee Buhr; Andrew R Buller; Zaid Afawi; Masahito Shimojo; Shingo Miyata; Shan Chen; Pedro Gonzalez-Alegre; Hilary L Griesbach; Shu Wu; Marcus Nashelsky; Eszter K Vladar; Dragana Antic; Polly J Ferguson; Sebahattin Cirak; Thomas Voit; Matthew P Scott; Jeffrey D Axelrod; Christina Gurnett; Azhar S Daoud; Sara Kivity; Miriam Y Neufeld; Aziz Mazarib; Rachel Straussberg; Simri Walid; Amos D Korczyn; Diane C Slusarski; Samuel F Berkovic; Hatem I El-Shanti Journal: Am J Hum Genet Date: 2008-10-30 Impact factor: 11.025
Authors: Elin Grundberg; Kerrin S Small; Åsa K Hedman; Alexandra C Nica; Alfonso Buil; Sarah Keildson; Jordana T Bell; Tsun-Po Yang; Eshwar Meduri; Amy Barrett; James Nisbett; Magdalena Sekowska; Alicja Wilk; So-Youn Shin; Daniel Glass; Mary Travers; Josine L Min; Sue Ring; Karen Ho; Gudmar Thorleifsson; Augustine Kong; Unnur Thorsteindottir; Chrysanthi Ainali; Antigone S Dimas; Neelam Hassanali; Catherine Ingle; David Knowles; Maria Krestyaninova; Christopher E Lowe; Paola Di Meglio; Stephen B Montgomery; Leopold Parts; Simon Potter; Gabriela Surdulescu; Loukia Tsaprouni; Sophia Tsoka; Veronique Bataille; Richard Durbin; Frank O Nestle; Stephen O'Rahilly; Nicole Soranzo; Cecilia M Lindgren; Krina T Zondervan; Kourosh R Ahmadi; Eric E Schadt; Kari Stefansson; George Davey Smith; Mark I McCarthy; Panos Deloukas; Emmanouil T Dermitzakis; Tim D Spector Journal: Nat Genet Date: 2012-09-02 Impact factor: 38.330
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Authors: Zubin H Patel; Xiaoming Lu; Daniel Miller; Carmy R Forney; Joshua Lee; Arthur Lynch; Connor Schroeder; Lois Parks; Albert F Magnusen; Xiaoting Chen; Mario Pujato; Avery Maddox; Erin E Zoller; Bahram Namjou; Hermine I Brunner; Michael Henrickson; Jennifer L Huggins; Adrienne H Williams; Julie T Ziegler; Mary E Comeau; Miranda C Marion; Stuart B Glenn; Adam Adler; Nan Shen; Swapan K Nath; Anne M Stevens; Barry I Freedman; Bernardo A Pons-Estel; Betty P Tsao; Chaim O Jacob; Diane L Kamen; Elizabeth E Brown; Gary S Gilkeson; Graciela S Alarcón; Javier Martin; John D Reveille; Juan-Manuel Anaya; Judith A James; Kathy L Sivils; Lindsey A Criswell; Luis M Vilá; Michelle Petri; R Hal Scofield; Robert P Kimberly; Jeffrey C Edberg; Rosalind Ramsey-Goldman; So-Young Bang; Hye-Soon Lee; Sang-Cheol Bae; Susan A Boackle; Deborah Cunninghame Graham; Timothy J Vyse; Joan T Merrill; Timothy B Niewold; Hannah C Ainsworth; Earl D Silverman; Michael H Weisman; Daniel J Wallace; Prithvi Raj; Joel M Guthridge; Patrick M Gaffney; Jennifer A Kelly; Marta E Alarcón-Riquelme; Carl D Langefeld; Edward K Wakeland; Kenneth M Kaufman; Matthew T Weirauch; John B Harley; Leah C Kottyan Journal: Hum Mol Genet Date: 2018-07-01 Impact factor: 5.121
Authors: Ting Li; He Li; Yue Li; Shu-An Dong; Ming Yi; Qiu-Xia Zhang; Bin Feng; Li Yang; Fu-Dong Shi; Chun-Sheng Yang Journal: Front Genet Date: 2021-07-21 Impact factor: 4.599