Daniel B Larach1, Milo C Engoren2, Ellen M Schmidt3, Michael Heung4. 1. Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: dlarach@med.umich.edu. 2. Departments of Anesthesiology, Division of Critical Care Medicine, and Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109, USA. 3. Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA. 4. Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract
PURPOSE: Limited data exists on potential genetic contributors to acute kidney injury. This review examines current knowledge of AKI genomics. MATERIALS AND METHODS: 32 studies were selected from PubMed and GWAS Catalog queries for original data studies of human AKI genetics. Hand search of references identified 3 additional manuscripts. RESULTS: 33 of 35 studies were hypothesis-driven investigations of candidate polymorphisms that either did not consistently replicate statistically significant findings, or obtained significant results only in few small-scale studies. Vote-counting meta-analysis of 9 variants examined in >1 candidate gene study showed ≥50% non-significant studies, with larger studies generally finding non-significant results. The remaining 2 studies were large-scale unbiased investigations: One examining 2,100 genes linked with cardiovascular, metabolic, and inflammatory syndromes identified BCL2, SERPINA4, and SIK3 variants, while a genome-wide association study (GWAS) identified variants in BBS9 and the GRM7|LMCD1-AS1 intergenic region. All studies had relatively small sample sizes (<2300 subjects). Study heterogeneity precluded candidate gene and GWA meta-analysis. CONCLUSIONS: Most studies of AKI genetics involve hypothesis-driven (rather than hypothesis-generating) candidate gene investigations that have failed to identify contributory variants consistently. A limited number of unbiased, larger-scale studies have been carried out, but there remains a pressing need for additional GWA studies.
PURPOSE: Limited data exists on potential genetic contributors to acute kidney injury. This review examines current knowledge of AKI genomics. MATERIALS AND METHODS: 32 studies were selected from PubMed and GWAS Catalog queries for original data studies of human AKI genetics. Hand search of references identified 3 additional manuscripts. RESULTS: 33 of 35 studies were hypothesis-driven investigations of candidate polymorphisms that either did not consistently replicate statistically significant findings, or obtained significant results only in few small-scale studies. Vote-counting meta-analysis of 9 variants examined in >1 candidate gene study showed ≥50% non-significant studies, with larger studies generally finding non-significant results. The remaining 2 studies were large-scale unbiased investigations: One examining 2,100 genes linked with cardiovascular, metabolic, and inflammatory syndromes identified BCL2, SERPINA4, and SIK3 variants, while a genome-wide association study (GWAS) identified variants in BBS9 and the GRM7|LMCD1-AS1 intergenic region. All studies had relatively small sample sizes (<2300 subjects). Study heterogeneity precluded candidate gene and GWA meta-analysis. CONCLUSIONS: Most studies of AKI genetics involve hypothesis-driven (rather than hypothesis-generating) candidate gene investigations that have failed to identify contributory variants consistently. A limited number of unbiased, larger-scale studies have been carried out, but there remains a pressing need for additional GWA studies.
Authors: Adam Lewis; Lisa Bastarache; Anita Pandit; Daniel B Larach; Jing He; Anik Sinha; Nicholas J Douville; Michael Heung; Michael R Mathis; Jonathan D Mosley; Jonathan P Wanderer; Sachin Kheterpal; Matthew Zawistowski; Chad M Brummett; Edward D Siew; Cassianne Robinson-Cohen; Miklos D Kertai Journal: BMC Nephrol Date: 2022-10-21 Impact factor: 2.585
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