Abstract: SA-PO401
A GWAS of Congenital Anomalies of the Kidney and Urinary Tract
Session Information
- Genetic Diseases of the Kidney - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Lim, Tze Yin, Columbia University, New York, New York, United States
- Ahram, Dina, Columbia University, New York, New York, United States
- Verbitsky, Miguel, Columbia University, New York, New York, United States
- Westland, Rik, VU University Medical Center, Amsterdam, Netherlands
- Krithivasan, Priya, Columbia University, New York, New York, United States
- Jin, Gina ying, Columbia University, New York, New York, United States
- Bodria, Monica, Giannina Gaslini Children's Hospital, Genoa, Italy
- Shril, Shirlee, Boston Childrens Hospital, Boston, Massachusetts, United States
- Kil, Byum hee, Columbia University, New York, New York, United States
- Fiaccadori, Enrico, Universita Degli Studi-Dip. Clinica Medica Nefrologia, Parma, Italy
- Masnata, Giuseppe, Azienda Ospedale G. Brotzu, Cagliari, Italy
- Saraga, Marijan, University Hospital in Split, Split, Croatia
- Mitrotti, Adele, Columbia University, New York, New York, United States
- Santoro, Domenico, Policlinico G Martino, Messina, Italy
- Lin, Fangming, Columbia University College of Physicians & Surgeons, New York, New York, United States
- Gesualdo, Loreto, University of Bari, Altamura, Bari, Italy
- Scolari, Francesco, University of Brescia, Montichiari (Brescia), Italy
- Tasic, Velibor, University Children's Hospital, Skopje, Macedonia (the former Yugoslav Republic of)
- Hildebrandt, Friedhelm, Boston Childrens Hospital, Boston, Massachusetts, United States
- Kiryluk, Krzysztof, Columbia University, New York, New York, United States
- Gharavi, Ali G., Columbia University, New York, New York, United States
- Sanna-Cherchi, Simone, Columbia University, New York, New York, United States
Background
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are prevalent causes of pediatric renal failure. We investigated common risk variants that may be involved in the pathogenesis of diverse CAKUT.
Methods
A Genome-Wide Association Study (GWAS) was conducted on 2,894 ethnically and clinically heterogeneous CAKUT cases and 15,589 genetically matched controls. Association tests were performed on the imputed dosages of 10 subpopulations under the additive model with population stratification corrected and meta-analyzed.
Results
We identified a significant association on chr.21q.21.1 (P=1.91 x10-9; OR=1.28) in CHODL, a gene that has been reported to be involved in motor axon differentiation in zebrafish models and has shown positive expression in the developing urogenital tract. We have found near genome-wide significant signals in 3 loci: TMEM229B (P=1.03 x10-7; OR=1.25), previously reported as a suggestive locus associated to renal function measures and chronic kidney disease in a GWAS in children; MARK1 (P=2.00 x10-7; OR=1.21), a gene possibly implicated in autism and expressed in the pre and postnatal urinary tract; and chr.5p15.31 (P=1.07x10-7; OR=1.43). Finally, we identified suggestive loci (P<1x10-5) within or near essential renal development genes in human and mouse model, including TWSG1, ROBO2, LAMA5, and GATA5.
Conclusion
Our preliminary GWAS identified CHODL as a novel CAKUT candidate gene, and have shown suggestive associations of variants in critical renal development genes. Integration with a subphenotype analysis may allow us to refine these loci and prioritize candidate susceptibility genes in CAKUT.
Funding
- NIDDK Support