ESPN 54th Annual Meeting

ESPN 2022


 
A genome-wide association study of the aetiology of solitary functioning kidney
SANDER GROEN IN T WOUD 1 CARLO MAJ 2 NEL ROELEVELD 1 WOUT FEITZ 3 MICHIEL SCHREUDER 4 LOES VAN DER ZANDEN 1

1- RADBOUD UNIVERSITY MEDICAL CENTER, DEPARTMENT FOR HEALTH EVIDENCE, RADBOUD INSTITUTE FOR HEALTH SCIENCES, NIJMEGEN, THE NETHERLANDS
2- INSTITUTE OF GENOMIC STATISTICS AND BIOINFORMATICS, UNIVERSITY HOSPITAL BONN, MEDICAL FACULTY UNIVERSITY OF BONN, BONN, GERMANY
3- RADBOUDUMC AMALIA CHILDREN’S HOSPITAL, DEPARTMENT OF UROLOGY, RADBOUD INSTITUTE FOR MOLECULAR LIFE SCIENCES, NIJMEGEN, THE NETHERLANDS
4- RADBOUDUMC AMALIA CHILDREN’S HOSPITAL, DEPARTMENT OF PEDIATRIC NEPHROLOGY, RADBOUD INSTITUTE FOR MOLECULAR LIFE SCIENCES, NIJMEGEN, THE NETHERLANDS
 
Introduction:

 Solitary functioning kidney (SFK) is a relatively common condition predisposing to kidney injury. Although several monogenic causes were identified, most cases cannot yet be explained. Therefore, its aetiology is likely multifactorial and several environmental risk factors have been reported, while common genetic variation may also contribute to genetic susceptibility. To identify common variants involved in the aetiology of SFK, we performed a genome-wide association study (GWAS).

Material and methods:

 A GWAS was performed using 702 patients with congenital SFK from the SOFIA study and 660 geographically matched controls from the AGORA data- and biobank. Phenotypic subgroups were created a priori. Association tests were performed in PLINK 2.0 on an imputed dataset under the assumption of an additive model. Principal component analyses were used to exclude ancestral outliers and control for population stratification. Results were analysed on individual SNP level with a fixed genome-wide significance threshold of 5 × 10-8 and on gene level using MAGMA with a significance threshold of 0.05/number of genes tested.

Results:

 In both the overall and subgroup analyses, no SNP reached the genome-wide significance threshold, with the top SNP at 6.3 × 10-7 in overall analyses and 9.3 × 10-8 in the MCDK subgroup. Analyses on gene level did not yield results above the significance threshold either, but candidate genes were identified that will be investigated further and results will be shared during the conference.

Conclusions:

 Our GWAS on the aetiology of SFK did not identify variants reaching genome-wide significance, most likely because of a lack of power. However, some of the identified variants may contribute to the genetic understanding of SFK and will be topic of further study.