TY - JOUR
T1 - Genome-wide CNV investigation suggests a role for cadherin, Wnt, and p53 pathways in primary open-angle glaucoma
AU - Lo Faro, Valeria
AU - ten Brink, Jacoline B.
AU - Snieder, Harold
AU - Jansonius, Nomdo M.
AU - Bergen, Arthur A.
N1 - Funding Information: This project was funded by European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No.675033 (EGRET plus). Additional funding was provided by the Rotterdamse Stichting Blindenbelangen (grant ID B20150036). The funding organization had no role in the design, conduct, analysis, or publication of this research. The Lifelines Biobank initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG the Netherlands), University of Groningen and the Northern Provinces of the Netherlands. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Background: To investigate whether copy number variations (CNVs) are implicated in molecular mechanisms underlying primary open-angle glaucoma (POAG), we used genotype data of POAG individuals and healthy controls from two case-control studies, AGS (n = 278) and GLGS-UGLI (n = 1292). PennCNV, QuantiSNP, and cnvPartition programs were used to detect CNV. Stringent quality controls at both sample and marker levels were applied. The identified CNVs were intersected in CNV region (CNVR). After, we performed burden analysis, CNV-genome-wide association analysis, gene set overrepresentation and pathway analysis. In addition, in human eye tissues we assessed the expression of the genes lying within significant CNVRs. Results: We reported a statistically significant greater burden of CNVs in POAG cases compared to controls (p-value = 0,007). In common between the two cohorts, CNV-association analysis identified statistically significant CNVRs associated with POAG that span 11 genes (APC, BRCA2, COL3A1, HLA-DRB1, HLA-DRB5, HLA-DRB6, MFSD8, NIPBL, SCN1A, SDHB, and ZDHHC11). Functional annotation and pathway analysis suggested the involvement of cadherin, Wnt signalling, and p53 pathways. Conclusions: Our data suggest that CNVs may have a role in the susceptibility of POAG and they can reveal more information on the mechanism behind this disease. Additional genetic and functional studies are warranted to ascertain the contribution of CNVs in POAG.
AB - Background: To investigate whether copy number variations (CNVs) are implicated in molecular mechanisms underlying primary open-angle glaucoma (POAG), we used genotype data of POAG individuals and healthy controls from two case-control studies, AGS (n = 278) and GLGS-UGLI (n = 1292). PennCNV, QuantiSNP, and cnvPartition programs were used to detect CNV. Stringent quality controls at both sample and marker levels were applied. The identified CNVs were intersected in CNV region (CNVR). After, we performed burden analysis, CNV-genome-wide association analysis, gene set overrepresentation and pathway analysis. In addition, in human eye tissues we assessed the expression of the genes lying within significant CNVRs. Results: We reported a statistically significant greater burden of CNVs in POAG cases compared to controls (p-value = 0,007). In common between the two cohorts, CNV-association analysis identified statistically significant CNVRs associated with POAG that span 11 genes (APC, BRCA2, COL3A1, HLA-DRB1, HLA-DRB5, HLA-DRB6, MFSD8, NIPBL, SCN1A, SDHB, and ZDHHC11). Functional annotation and pathway analysis suggested the involvement of cadherin, Wnt signalling, and p53 pathways. Conclusions: Our data suggest that CNVs may have a role in the susceptibility of POAG and they can reveal more information on the mechanism behind this disease. Additional genetic and functional studies are warranted to ascertain the contribution of CNVs in POAG.
KW - CNV
KW - Cell adhesion
KW - Primary open-angle glaucoma
KW - WNT signalling
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=85111958206&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s12864-021-07846-1
DO - https://doi.org/10.1186/s12864-021-07846-1
M3 - Article
C2 - 34348663
SN - 1471-2164
VL - 22
JO - BMC Genomics
JF - BMC Genomics
IS - 1
M1 - 590
ER -