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in European SLE","volume":"15","author":"DL Morris","year":"2014","journal-title":"Genes Immun"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"E79","DOI":"10.1097\/mib.0b013e318280e790","article-title":"Haplotype-tagging analysis of common variants of the IL23R gene demonstrates gene-wide extent of association with IBD","volume":"19","author":"J Van Limbergen","year":"2013","journal-title":"Inflamm Bowel Dis"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1038\/ajg.2013.354","article-title":"EMerging BiomARKers in Inflammatory Bowel Disease (EMBARK) study identifies fecal calprotectin, serum MMP9, and serum IL-22 as a novel combination of biomarkers for Crohn's disease activity: role of cross-sectional imaging","volume":"108","author":"WA Faubion Jr.","year":"2013","journal-title":"Am J Gastroenterol"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"14747","DOI":"10.1073\/pnas.0706645104","article-title":"Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci","volume":"104","author":"JV Raelson","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1093\/genetics\/164.4.1567","article-title":"Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies","volume":"164","author":"D Falush","year":"2003","journal-title":"Genetics"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"575","DOI":"10.2119\/2008-00056.Liu","article-title":"Genome-wide association scan identifies candidate polymorphisms associated with differential response to anti-TNF treatment in rheumatoid arthritis","volume":"14","author":"C Liu","year":"2008","journal-title":"Mol Med"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1002\/art.30130","article-title":"Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci","volume":"63","author":"D Plant","year":"2011","journal-title":"Arthritis Rheum"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.autrev.2005.07.006","article-title":"The CORRONA database","volume":"5","author":"JM Kremer","year":"2006","journal-title":"Autoimmun Rev"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"e278","DOI":"10.1371\/journal.pmed.0040278","article-title":"A candidate gene approach identifies the TRAF1\/C5 region as a risk factor for rheumatoid arthritis","volume":"4","author":"FA Kurreeman","year":"2007","journal-title":"PLoS Med"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1136\/ard.2007.074104","article-title":"A single tumour necrosis factor haplotype influences the response to adalimumab in rheumatoid arthritis","volume":"67","author":"C Miceli-Richard","year":"2008","journal-title":"Ann Rheum Dis"},{"key":"ref87","first-page":"45","article-title":"Reuma.pt\u2014the rheumatic diseases portuguese register","volume":"36","author":"H Canhao","year":"2011","journal-title":"Acta Reumatol Port"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1101\/gr.129684.111","article-title":"VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing","volume":"22","author":"DC Koboldt","year":"2012","journal-title":"Genome Res"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"K Wang","year":"2010","journal-title":"Nucleic acids research"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ajhg.2010.12.007","article-title":"Genetic basis of autoantibody positive and negative rheumatoid arthritis risk in a multi-ethnic cohort derived from electronic health records","volume":"88","author":"F Kurreeman","year":"2011","journal-title":"Am J Hum Genet"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1136\/annrheumdis-2012-203202","article-title":"Association between low density lipoprotein and rheumatoid arthritis genetic factors with low density lipoprotein levels in rheumatoid arthritis and non-rheumatoid arthritis controls","volume":"73","author":"KP Liao","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1001\/jama.2012.13260","article-title":"Trends in lipids and lipoproteins in US adults, 1988\u20132010","volume":"308","author":"MD Carroll","year":"2012","journal-title":"JAMA"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1093\/bioinformatics\/19.1.149","article-title":"Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits","volume":"19","author":"S Purcell","year":"2003","journal-title":"Bioinformatics"}],"container-title":["PLOS 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