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A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases
DC Field | Value | Language |
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dc.contributor.author | Han, Buhm | - |
dc.contributor.author | Pouget, Jennie G. | - |
dc.contributor.author | Slowikowski, Kamil | - |
dc.contributor.author | Stahl, Eli | - |
dc.contributor.author | Lee, Cue Hyunkyu | - |
dc.contributor.author | Diogo, Dorothee | - |
dc.contributor.author | Hu, Xinli | - |
dc.contributor.author | Park, Yu Rang | - |
dc.contributor.author | Kim, Eunji | - |
dc.contributor.author | Gregersen, Peter K. | - |
dc.contributor.author | Dahlqvist, Solbritt Rantapaa | - |
dc.contributor.author | Worthington, Jane | - |
dc.contributor.author | Martin, Javier | - |
dc.contributor.author | Eyre, Steve | - |
dc.contributor.author | Klareskog, Lars | - |
dc.contributor.author | Huizinga, Tom | - |
dc.contributor.author | Chen, Wei-Min | - |
dc.contributor.author | Onengut-Gumuscu, Suna | - |
dc.contributor.author | Rich, Stephen S. | - |
dc.contributor.author | Wray, Naomi R. | - |
dc.contributor.author | Raychaudhuri, Soumya | - |
dc.date.accessioned | 2023-04-26T05:09:32Z | - |
dc.date.available | 2023-04-26T05:09:32Z | - |
dc.date.created | 2018-09-21 | - |
dc.date.created | 2018-09-21 | - |
dc.date.created | 2018-09-21 | - |
dc.date.created | 2018-09-21 | - |
dc.date.issued | 2016-07 | - |
dc.identifier.citation | Nature Genetics, Vol.48 No.7, pp.803-810 | - |
dc.identifier.issn | 1061-4036 | - |
dc.identifier.uri | https://hdl.handle.net/10371/191578 | - |
dc.description.abstract | There is growing evidence of shared risk alleles for complex traits (pleiotropy), including autoimmune and neuropsychiatric diseases. This might be due to sharing among all individuals (whole-group pleiotropy) or a subset of individuals in a genetically heterogeneous cohort (subgroup heterogeneity). Here we describe the use of a well-powered statistic, BUHMBOX, to distinguish between those two situations using genotype data. We observed a shared genetic basis for 11 autoimmune diseases and type 1 diabetes (T1D; P < 1 x 10(-4)) and for 11 autoimmune diseases and rheumatoid arthritis (RA; P < 1 x 10(-3)). This sharing was not explained by subgroup heterogeneity (corrected P-BUHMBOX > 0.2; 6,670 T1D cases and 7,279 RA cases). Genetic sharing between seronegative and seropostive RA (P < 1 x 10(-9)) had significant evidence of subgroup heterogeneity, suggesting a subgroup of seropositive-like cases within seronegative cases (P-BUHMBOX = 0.008; 2,406 seronegative RA cases). We also observed a shared genetic basis for major depressive disorder (MDD) and schizophrenia (P < 1 x 10(-4)) that was not explained by subgroup heterogeneity (P-BUHMBOX = 0.28; 9,238 MDD cases). | - |
dc.language | 영어 | - |
dc.publisher | Nature Publishing Group | - |
dc.title | A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/ng.3572 | - |
dc.citation.journaltitle | Nature Genetics | - |
dc.identifier.wosid | 000378840100019 | - |
dc.identifier.scopusid | 2-s2.0-84968627067 | - |
dc.citation.endpage | 810 | - |
dc.citation.number | 7 | - |
dc.citation.startpage | 803 | - |
dc.citation.volume | 48 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Han, Buhm | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | GENOME-WIDE ASSOCIATION | - |
dc.subject.keywordPlus | INFLAMMATORY-BOWEL-DISEASE | - |
dc.subject.keywordPlus | RHEUMATOID-ARTHRITIS | - |
dc.subject.keywordPlus | DIAGNOSTIC MISCLASSIFICATION | - |
dc.subject.keywordPlus | GENETIC CORRELATIONS | - |
dc.subject.keywordPlus | SUSCEPTIBILITY LOCI | - |
dc.subject.keywordPlus | MAJOR DEPRESSION | - |
dc.subject.keywordPlus | COMPLEX DISEASES | - |
dc.subject.keywordPlus | VARIANTS | - |
dc.subject.keywordPlus | DISORDER | - |
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