TY - JOUR
T1 - A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney
AU - Westland, R.
AU - on behalf of the SOFIA Study Group
AU - Groen in ’t Woud, Sander
AU - Maj, Carlo
AU - Renkema, Kirsten Y.
AU - Galesloot, Tessel
AU - van Rooij, Iris A. L. M.
AU - Vermeulen, Sita H.
AU - Feitz, Wout F. J.
AU - Roeleveld, Nel
AU - Schreuder, Michiel F.
AU - van der Zanden, Loes F. M.
N1 - Funding Information: This research was funded by a Junior Investigator Grant from the Radboud Institute for Health Sciences. Loes van der Zanden is funded by a Veni grant (91618036) from the Dutch Research Council (NWO). Loes van der Zanden and Sander Groen in ’t Woud are funded by a Consortium grant from the Dutch Kidney Foundation (20OC002). Michiel Schreuder is funded by a Vidi grant (016.156.454) from the Dutch Research Council (NWO). Kirsten Renkema is funded by a Kolff Senior grant (15OKG18) from the Dutch Kidney Foundation. Publisher Copyright: © 2022 by the authors.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Congenital solitary functioning kidney (CSFK) is a birth defect that occurs in 1:1500 children and predisposes them to kidney injury. Its aetiology is likely multifactorial. In addition to known monogenic causes and environmental risk factors, common genetic variation may contribute to susceptibility to CSFK. We performed a genome-wide association study among 452 patients with CSFK and two control groups of 669 healthy children and 5363 unaffected adults. Variants in two loci reached the genome-wide significance threshold of 5 × 10−8, and variants in 30 loci reached the suggestive significance threshold of 1 × 10−5. Of these, an identified locus with lead single nucleotide variant (SNV) rs140804918 (odds ratio 3.1, p-value = 1.4 × 10−8) on chromosome 7 was most promising due to its close proximity to HGF, a gene known to be involved in kidney development. Based on their known molecular functions, both KCTD20 and STK38 could explain the suggestive significant association with lead SNV rs148413365 on chromosome 6. Our findings need replication in an independent cohort of CSFK patients before they can be established definitively. However, our analysis suggests that common variants play a role in CSFK aetiology. Future research could enhance our understanding of the molecular mechanisms involved.
AB - Congenital solitary functioning kidney (CSFK) is a birth defect that occurs in 1:1500 children and predisposes them to kidney injury. Its aetiology is likely multifactorial. In addition to known monogenic causes and environmental risk factors, common genetic variation may contribute to susceptibility to CSFK. We performed a genome-wide association study among 452 patients with CSFK and two control groups of 669 healthy children and 5363 unaffected adults. Variants in two loci reached the genome-wide significance threshold of 5 × 10−8, and variants in 30 loci reached the suggestive significance threshold of 1 × 10−5. Of these, an identified locus with lead single nucleotide variant (SNV) rs140804918 (odds ratio 3.1, p-value = 1.4 × 10−8) on chromosome 7 was most promising due to its close proximity to HGF, a gene known to be involved in kidney development. Based on their known molecular functions, both KCTD20 and STK38 could explain the suggestive significant association with lead SNV rs148413365 on chromosome 6. Our findings need replication in an independent cohort of CSFK patients before they can be established definitively. However, our analysis suggests that common variants play a role in CSFK aetiology. Future research could enhance our understanding of the molecular mechanisms involved.
KW - aetiology
KW - congenital anomalies of the kidney and urinary tract (CAKUT)
KW - genome-wide association study
KW - kidney development
KW - kidney hypodysplasia
KW - multicystic dysplastic kidney
KW - single nucleotide variant
KW - solitary functioning kidney
KW - unilateral kidney agenesis
UR - http://www.scopus.com/inward/record.url?scp=85144687236&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85144687236&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36551779
U2 - https://doi.org/10.3390/biomedicines10123023
DO - https://doi.org/10.3390/biomedicines10123023
M3 - Article
C2 - 36551779
SN - 2227-9059
VL - 10
JO - Biomedicines
JF - Biomedicines
IS - 12
M1 - 3023
ER -