Novel risk genes for systemic lupus erythematosus predicted by random forest classification.

Autor:	Almlöf JC; Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. jonas.carlsson@medsci.uu.se., Alexsson A; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Imgenberg-Kreuz J; Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Sylwan L; Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.; Science for Life Laboratory (SciLifeLab), Department of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden., Bäcklin C; Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Leonard D; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Nordmark G; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Tandre K; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Eloranta ML; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Padyukov L; Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska university hospital, Stockholm, Sweden., Bengtsson C; Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden., Jönsen A; Lund University, Skåne University Hospital, Department of Clinical Sciences, Rheumatology, Lund, Sweden., Dahlqvist SR; Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden., Sjöwall C; AIR/Rheumatology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden., Bengtsson AA; Lund University, Skåne University Hospital, Department of Clinical Sciences, Rheumatology, Lund, Sweden., Gunnarsson I; Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska university hospital, Stockholm, Sweden., Svenungsson E; Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska university hospital, Stockholm, Sweden., Rönnblom L; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Sandling JK; Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Syvänen AC; Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2017 Jul 24; Vol. 7 (1), pp. 6236. Date of Electronic Publication: 2017 Jul 24.
DOI:	10.1038/s41598-017-06516-1
Abstrakt:	Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual's SLE risk we designed a random forest classifier using SNP genotype data generated on the "Immunochip" from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu