{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:23:20Z","timestamp":1791300200809,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,1,9]],"date-time":"2014-01-09T00:00:00Z","timestamp":1389225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"Summary<\/jats:title>\n \n Over the last decade, significant technological breakthroughs have revolutionized human genomic research in the form of genome\u2010wide association studies (\n GWAS<\/jats:styled-content>\n s).\n GWAS<\/jats:styled-content>\n s have identified thousands of statistically significant genetic variants associated with hundreds of human conditions including many with immunological aetiologies (e.g. multiple sclerosis, ankylosing spondylitis and rheumatoid arthritis). Unfortunately, most\n GWAS<\/jats:styled-content>\n s fail to identify clinically significant associations. Identifying biologically significant variants by\n GWAS<\/jats:styled-content>\n also presents a challenge. The\n GWAS<\/jats:styled-content>\n is a phenotype\u2010to\u2010genotype approach. As a complementary\/alternative approach to the\n GWAS<\/jats:styled-content>\n , investigators have begun to exploit extensive electronic medical record systems to conduct a genotype\u2010to\u2010phenotype approach when studying human disease\u00a0\u2013\u00a0specifically, the phenome\u2010wide association study (\n P<\/jats:styled-content>\n he\n WAS<\/jats:styled-content>\n ). Although the Phe\n WAS<\/jats:styled-content>\n approach is in its infancy, this method has already demonstrated its capacity to rediscover important genetic associations related to immunological diseases\/conditions. Furthermore,\n P<\/jats:styled-content>\n he\n WAS<\/jats:styled-content>\n has the advantage of identifying genetic variants with pleiotropic properties. This is particularly relevant for\n \n HLA<\/jats:styled-content>\n <\/jats:italic>\n variants. For example,\n P<\/jats:styled-content>\n he\n WAS<\/jats:styled-content>\n results have demonstrated that the\n \n HLA<\/jats:styled-content>\n \u2010\n DRB<\/jats:styled-content>\n 1\n <\/jats:italic>\n variant associated with multiple sclerosis may also be associated with erythematous conditions including rosacea. Likewise,\n P<\/jats:styled-content>\n he\n WAS<\/jats:styled-content>\n has demonstrated that the\n \n HLA<\/jats:styled-content>\n \u2010\n B<\/jats:styled-content>\n <\/jats:italic>\n genotype is not only associated with spondylopathies, uveitis, and variability in platelet count, but may also play an important role in other conditions, such as mastoiditis. This review will discuss and compare general\n P<\/jats:styled-content>\n he\n WAS<\/jats:styled-content>\n methodologies, describe both the challenges and advantages of the\n P<\/jats:styled-content>\n he\n WAS<\/jats:styled-content>\n , and provide insight into the potential directions in which\n P<\/jats:styled-content>\n he\n WAS<\/jats:styled-content>\n may lead.\n <\/jats:p>","DOI":"10.1111\/imm.12195","type":"journal-article","created":{"date-parts":[[2013,10,22]],"date-time":"2013-10-22T03:01:01Z","timestamp":1382410861000},"page":"157-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":145,"title":["The challenges, advantages and future of phenome\u2010wide association studies"],"prefix":"10.1111","volume":"141","author":[{"given":"Scott J.","family":"Hebbring","sequence":"first","affiliation":[{"name":"Center for Human Genetics Marshfield Clinic Research Foundation Marshfield WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35057062"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058040"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04226"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06258"},{"key":"e_1_2_9_6_1","unstructured":"HindorffLA MacArthurJ MoralesJ JunkinsHA HallPN KlemmAK ManolioTA.A Catalog of Published Genome\u2010Wide Association Studies. 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