Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome.
Alleles
Androgen-Binding Protein
/ genetics
Calcium Channels
/ genetics
Child
Databases, Factual
Epitopes
/ chemistry
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
HLA-DQ alpha-Chains
/ genetics
HLA-DQ beta-Chains
/ genetics
HLA-DRB1 Chains
/ genetics
Humans
Immune System
Male
Membrane Glycoproteins
/ genetics
Nephrotic Syndrome
/ drug therapy
Odds Ratio
Peptides
/ chemistry
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Steroids
/ therapeutic use
CALHM6
FAM26F
GWAS
HLA
SSNS
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
28
10
2018
accepted:
22
04
2019
pubmed:
3
7
2019
medline:
28
4
2020
entrez:
3
7
2019
Statut:
ppublish
Résumé
Steroid-sensitive nephrotic syndrome (SSNS), the most common form of nephrotic syndrome in childhood, is considered an autoimmune disease with an established classic HLA association. However, the precise etiology of the disease is unclear. In other autoimmune diseases, the identification of loci outside the classic HLA region by genome-wide association studies (GWAS) has provided critical insights into disease pathogenesis. Previously conducted GWAS of SSNS have not identified non-HLA loci achieving genome-wide significance. In an attempt to identify additional loci associated with SSNS, we conducted a GWAS of a large cohort of European ancestry comprising 422 ethnically homogeneous pediatric patients and 5642 ethnically matched controls. The GWAS found three loci that achieved genome-wide significance, which explain approximately 14% of the genetic risk for SSNS. It confirmed the previously reported association with the HLA-DR/DQ region (lead single-nucleotide polymorphism [SNP] rs9273542, Because
Sections du résumé
BACKGROUND
Steroid-sensitive nephrotic syndrome (SSNS), the most common form of nephrotic syndrome in childhood, is considered an autoimmune disease with an established classic HLA association. However, the precise etiology of the disease is unclear. In other autoimmune diseases, the identification of loci outside the classic HLA region by genome-wide association studies (GWAS) has provided critical insights into disease pathogenesis. Previously conducted GWAS of SSNS have not identified non-HLA loci achieving genome-wide significance.
METHODS
In an attempt to identify additional loci associated with SSNS, we conducted a GWAS of a large cohort of European ancestry comprising 422 ethnically homogeneous pediatric patients and 5642 ethnically matched controls.
RESULTS
The GWAS found three loci that achieved genome-wide significance, which explain approximately 14% of the genetic risk for SSNS. It confirmed the previously reported association with the HLA-DR/DQ region (lead single-nucleotide polymorphism [SNP] rs9273542,
CONCLUSIONS
Because
Identifiants
pubmed: 31263063
pii: ASN.2018101054
doi: 10.1681/ASN.2018101054
pmc: PMC6683715
doi:
Substances chimiques
Androgen-Binding Protein
0
CALHM6 protein, human
0
Calcium Channels
0
Epitopes
0
HLA-DQ alpha-Chains
0
HLA-DQ beta-Chains
0
HLA-DRB1 Chains
0
Membrane Glycoproteins
0
PARM-1 protein, human
0
Peptides
0
Steroids
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1375-1384Subventions
Organisme : Medical Research Council
ID : G1002528
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK094987
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK098135
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
Copyright © 2019 by the American Society of Nephrology.
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