File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Genome-wide assessment of genetic risk for systemic lupus erythematosus and disease severity

TitleGenome-wide assessment of genetic risk for systemic lupus erythematosus and disease severity
Authors
Keywordskidney diseases
systemic lupus erythematosus
age of onset
genome
lupus nephritis
Issue Date2020
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2020, v. 29, p. 1745-1756 How to Cite?
AbstractUsing three European and two Chinese genome-wide association studies (GWAS), we investigated the performance of genetic risk scores (GRSs) for predicting the susceptibility and severity of systemic lupus erythematosus (SLE), using renal disease as a proxy for severity. We used four GWASs to test the performance of GRS both cross validating within the European population and between European and Chinese populations. The performance of GRS in SLE risk prediction was evaluated by receiver operating characteristic (ROC) curves. We then analyzed the polygenic nature of SLE statistically. We also partitioned patients according to their age-of-onset and evaluated the predictability of GRS in disease severity in each age group. We found consistently that the best GRS in the prediction of SLE used SNPs associated at the level of P < 1e−05 in all GWAS data sets and that SNPs with P-values above 0.2 were inflated for SLE true positive signals. The GRS results in an area under the ROC curve ranging between 0.64 and 0.72, within European and between the European and Chinese populations. We further showed a significant positive correlation between a GRS and renal disease in two independent European GWAS (Pcohort1 = 2.44e−08; Pcohort2 = 0.00205) and a significant negative correlation with age of SLE onset (Pcohort1 = 1.76e−12; Pcohort2 = 0.00384). We found that the GRS performed better in the prediction of renal disease in the ‘later onset’ compared with the ‘earlier onset’ group. The GRS predicts SLE in both European and Chinese populations and correlates with poorer prognostic factors: young age-of-onset and lupus nephritis.
Persistent Identifierhttp://hdl.handle.net/10722/285479
ISSN
2020 Impact Factor: 6.15
2015 SCImago Journal Rankings: 4.288
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, L-
dc.contributor.authorWang, YF-
dc.contributor.authorLiu, L-
dc.contributor.authorBielowka, A-
dc.contributor.authorAhmed, R-
dc.contributor.authorZHANG, H-
dc.contributor.authorTombleson, P-
dc.contributor.authorRoberts, AL-
dc.contributor.authorOdhams, CA-
dc.contributor.authorCunninghame, D-
dc.contributor.authorZhang, X-
dc.contributor.authorYang, W-
dc.contributor.authorVyse, TJ-
dc.contributor.authorMorris, DL-
dc.date.accessioned2020-08-18T03:53:48Z-
dc.date.available2020-08-18T03:53:48Z-
dc.date.issued2020-
dc.identifier.citationHuman Molecular Genetics, 2020, v. 29, p. 1745-1756-
dc.identifier.issn0964-6906-
dc.identifier.urihttp://hdl.handle.net/10722/285479-
dc.description.abstractUsing three European and two Chinese genome-wide association studies (GWAS), we investigated the performance of genetic risk scores (GRSs) for predicting the susceptibility and severity of systemic lupus erythematosus (SLE), using renal disease as a proxy for severity. We used four GWASs to test the performance of GRS both cross validating within the European population and between European and Chinese populations. The performance of GRS in SLE risk prediction was evaluated by receiver operating characteristic (ROC) curves. We then analyzed the polygenic nature of SLE statistically. We also partitioned patients according to their age-of-onset and evaluated the predictability of GRS in disease severity in each age group. We found consistently that the best GRS in the prediction of SLE used SNPs associated at the level of P < 1e−05 in all GWAS data sets and that SNPs with P-values above 0.2 were inflated for SLE true positive signals. The GRS results in an area under the ROC curve ranging between 0.64 and 0.72, within European and between the European and Chinese populations. We further showed a significant positive correlation between a GRS and renal disease in two independent European GWAS (Pcohort1 = 2.44e−08; Pcohort2 = 0.00205) and a significant negative correlation with age of SLE onset (Pcohort1 = 1.76e−12; Pcohort2 = 0.00384). We found that the GRS performed better in the prediction of renal disease in the ‘later onset’ compared with the ‘earlier onset’ group. The GRS predicts SLE in both European and Chinese populations and correlates with poorer prognostic factors: young age-of-onset and lupus nephritis.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/-
dc.relation.ispartofHuman Molecular Genetics-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectkidney diseases-
dc.subjectsystemic lupus erythematosus-
dc.subjectage of onset-
dc.subjectgenome-
dc.subjectlupus nephritis-
dc.titleGenome-wide assessment of genetic risk for systemic lupus erythematosus and disease severity-
dc.typeArticle-
dc.identifier.emailWang, YF: yfwangbm@connect.hku.hk-
dc.identifier.emailYang, W: yangwl@hku.hk-
dc.identifier.authorityYang, W=rp00524-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1093/hmg/ddaa030-
dc.identifier.pmid32077931-
dc.identifier.pmcidPMC7322569-
dc.identifier.scopuseid_2-s2.0-85087320735-
dc.identifier.hkuros312931-
dc.identifier.volume29-
dc.identifier.spage1745-
dc.identifier.epage1756-
dc.identifier.isiWOS:000562462000013-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl0964-6906-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats