Exome Sequencing Identifies Susceptibility Loci for Sarcoidosis Prognosis
Many sarcoidosis-associating immunological genes have been shown to be shared between other immune-mediated diseases. In Finnish sarcoidosis patients, good prognosis subjects more commonly have HLA-DRB1*03:01 and/or HLA-DRB1*04:01-DPB1*04:01 haplotype, but no marker for persistent disease have been...
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doaj-bd21db0b3bf446a7930a9ec827546d102020-11-25T02:10:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-12-011010.3389/fimmu.2019.02964489716Exome Sequencing Identifies Susceptibility Loci for Sarcoidosis PrognosisElisa Lahtela0Matti Kankainen1Matti Kankainen2Juha Sinisalo3Olof Selroos4Marja-Liisa Lokki5Transplantation Laboratory, Department of Pathology, University of Helsinki, Helsinki, FinlandInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, FinlandMedical and Clinical Genetics, Helsinki University Hospital, University of Hesinki, Helsinki, FinlandHeart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandUniversity of Helsinki, Helsinki, FinlandTransplantation Laboratory, Department of Pathology, University of Helsinki, Helsinki, FinlandMany sarcoidosis-associating immunological genes have been shown to be shared between other immune-mediated diseases. In Finnish sarcoidosis patients, good prognosis subjects more commonly have HLA-DRB1*03:01 and/or HLA-DRB1*04:01-DPB1*04:01 haplotype, but no marker for persistent disease have been found. The objective was to further pinpoint genetic differences between prognosis subgroups in relation to the HLA markers. Whole-exome sequencing was conducted for 72 patients selected based on disease activity (resolved disease, n = 36; persistent disease, n = 36). Both groups were further divided by the HLA markers (one/both markers, n = 18; neither of the markers, n = 18). The Finnish exome data from the Genome Aggregation Database was used as a control population in the WES sample. Statistical analyses included single-variant analysis for common variants and gene level analysis for rare variants. We attempted to replicate associated variants in 181 Finnish sarcoidosis patients and 150 controls. An association was found in chromosome 1p36.21 (AADACL3 and C1orf158), which has recently been associated with sarcoidosis in another WES study. In our study, variations in these genes were associated with resolved disease (AADACL3, p = 0.0001 and p = 0.0003; C1orf158, p = 7.03E-05). Another interesting chromosomal region also peaked, Leucocyte Receptor Complex in 19q13.42, but the association diminished in the replication sample. In conclusion, this WES study supports the previously found association in the region 1p36.21. Furthermore, a novel to sarcoidosis region was found, but additional studies are warranted to verify this association.https://www.frontiersin.org/article/10.3389/fimmu.2019.02964/fullsarcoidosisprognosisMHCwhole exome sequencing1p36.21leucocyte receptor complex |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elisa Lahtela Matti Kankainen Matti Kankainen Juha Sinisalo Olof Selroos Marja-Liisa Lokki |
spellingShingle |
Elisa Lahtela Matti Kankainen Matti Kankainen Juha Sinisalo Olof Selroos Marja-Liisa Lokki Exome Sequencing Identifies Susceptibility Loci for Sarcoidosis Prognosis Frontiers in Immunology sarcoidosis prognosis MHC whole exome sequencing 1p36.21 leucocyte receptor complex |
author_facet |
Elisa Lahtela Matti Kankainen Matti Kankainen Juha Sinisalo Olof Selroos Marja-Liisa Lokki |
author_sort |
Elisa Lahtela |
title |
Exome Sequencing Identifies Susceptibility Loci for Sarcoidosis Prognosis |
title_short |
Exome Sequencing Identifies Susceptibility Loci for Sarcoidosis Prognosis |
title_full |
Exome Sequencing Identifies Susceptibility Loci for Sarcoidosis Prognosis |
title_fullStr |
Exome Sequencing Identifies Susceptibility Loci for Sarcoidosis Prognosis |
title_full_unstemmed |
Exome Sequencing Identifies Susceptibility Loci for Sarcoidosis Prognosis |
title_sort |
exome sequencing identifies susceptibility loci for sarcoidosis prognosis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-12-01 |
description |
Many sarcoidosis-associating immunological genes have been shown to be shared between other immune-mediated diseases. In Finnish sarcoidosis patients, good prognosis subjects more commonly have HLA-DRB1*03:01 and/or HLA-DRB1*04:01-DPB1*04:01 haplotype, but no marker for persistent disease have been found. The objective was to further pinpoint genetic differences between prognosis subgroups in relation to the HLA markers. Whole-exome sequencing was conducted for 72 patients selected based on disease activity (resolved disease, n = 36; persistent disease, n = 36). Both groups were further divided by the HLA markers (one/both markers, n = 18; neither of the markers, n = 18). The Finnish exome data from the Genome Aggregation Database was used as a control population in the WES sample. Statistical analyses included single-variant analysis for common variants and gene level analysis for rare variants. We attempted to replicate associated variants in 181 Finnish sarcoidosis patients and 150 controls. An association was found in chromosome 1p36.21 (AADACL3 and C1orf158), which has recently been associated with sarcoidosis in another WES study. In our study, variations in these genes were associated with resolved disease (AADACL3, p = 0.0001 and p = 0.0003; C1orf158, p = 7.03E-05). Another interesting chromosomal region also peaked, Leucocyte Receptor Complex in 19q13.42, but the association diminished in the replication sample. In conclusion, this WES study supports the previously found association in the region 1p36.21. Furthermore, a novel to sarcoidosis region was found, but additional studies are warranted to verify this association. |
topic |
sarcoidosis prognosis MHC whole exome sequencing 1p36.21 leucocyte receptor complex |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02964/full |
work_keys_str_mv |
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