1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function

Kronenberg, Florian; Most, Peter J. van der; Teumer, Alexander; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Nolte, Ilja M.; Cocca, Massimiliano; Taliun, Daniel; Gomez, Felicia; Li, Yong; Tayo, Bamidele O.; Tin, Adrienne; Feitosa, Mary F.; Aspelund, Thor; Attia, John; Biffar, Reiner; Bochud, Murielle; Boerwinkle, Eric; Borecki, Ingrid B.; Böttinger, Erwin P.; Chen, Ming-Huei; Chouraki, Vincent; Ciullo, Marina; Coresh, Josef; Cornelis, Marilyn C.; Curhan, Gary C.; D’Adamo, Pio; Dehghan, Abbas; Dengler, Laura; Ding, Jingzhong; Eiríksdóttir, Guðný; Endlich, Karlhans; Enroth, Stefan; Esko, Tõnu; Franco, Oscar H.; Gasparini, Paolo; Gieger, Christian; Girotto, Giorgia; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Hancock, Stephen; Harris, Tamara B.; Helmer, Catherine; Höllerer, Simon; Hofer, Edith; Hofman, Albert; Holliday, Elizabeth G.; Homuth, Georg; Hu, Frank B.; Huth, Cornelia; Hutri‐Kähönen, Nina; Hwang, Shih Jen; Imboden, Medea; Johansson, Åsa; Kähönen, Mika; König, Wolfgang; Kramer, Holly; Krämer, Bernhard K.; Kumar, Ashish; Kutalik, Zoltán; Lambert, Jean‐Charles; Launer, Lenore J.; Lehtimäki, Terho; Borst, Martin H. de; Navis, Gerjan; Swertz, Morris A.; Liu, Yongmei; Lohman, Kurt; Loos, Ruth J.F.; Lu, Yingchang; Lyytikäinen, Leo Pekka; McEvoy, Mark; Meisinger, Christa; Meitinger, Thomas; Metspalu, Andres; Metzger, Marie; Mihailov, Evelin; Mitchell, Paul; Nauck, Matthias; Oldehinkel, Albertine J.; Olden, Matthias; Penninx, Brenda W. J. H.; Pistis, Giorgio; Pramstaller, Peter P.; Probst‐Hensch, Nicole; Raitakari, Olli T.; Rettig, Rainer; Ridker, Paul M.; Rivadeneira, Fernando; Robino, Antonietta; Rosas, Sylvia E.; Ruderfer, Douglas M.; Ruggiero, Daniela; Saba, Yasaman; Sala, Cinzia; Schmidt, Helena; Schmidt, Reinhold; Scott, Rodney J.; Sedaghat, Sanaz; Smith, Albert V.; Sorice, Rossella; Stengel, Bénédicte; Stracke, Sylvia; Strauch, Konstantin; Toniolo, Daniela; Uitterlinden, André G.; Ulivi, Sheila; Viikari, Jorma; Völker, Uwe; Vollenweider, Péter; Völzke, Henry; Vuckovic, Dragana; Waldenberger, Mélanie; Wang, Jie Jin; Yang, Qiong; Chasman, Daniel I.; Tromp, Gerard; Snieder, Harold; Heid, Iris M.; Fox, Caroline S.; Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A.; Fuchsberger, Christian

doi:10.1038/srep45040

Cited by 100 publications

(116 citation statements)

References 53 publications

(102 reference statements)

Supporting

Mentioning

110

Contrasting

Order By: Relevance

“…30 More importantly, a recent GWAS by Gorski and colleagues identified that the ARL15 gene was associated with kidney function. 31 Considering the importance of kidney function in BP regulation and potassium filtration, further investigation into this gene is warranted. While the functional relevance of ARL15 to BP is unclear, this signal could reflect other genes at this locus.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Gene–Potassium Interaction Analyses on Blood Pressure

Chen

et al. 2017

Circ Cardiovasc Genet

View full text Add to dashboard Cite

Background Gene environmental interaction analysis can identify novel genetic factors for blood pressure. We performed genome-wide analyses to identify genomic loci that interact with potassium to influence blood pressure (BP) using single marker (one and two degrees of freedom [DF] joint tests) and gene-based tests among Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Methods and Results Among 1,876 GenSalt participants, the average of three urine samples was used to estimate potassium excretion. Nine BP measurements were taken using a random-zero-sphygmomanometer. A total of 2.2 million SNPs were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P <1.00×10−4) from GenSalt were evaluated for replication among 775 Chinese participants of the Multi-ethnic Study of Atherosclerosis (MESA). SNP and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The one DF tests identified interactions for ARL15 rs16882447 on systolic BP (P=2.83×10−9) and RANBP3L rs958929 on pulse pressure (P=1.58×10−8). The two DF tests confirmed the ARL15 rs16882447 signal for systolic BP (P=1.15×10−9). Genome-wide gene-based analysis identified CC2D2A (P=2.59×10−7) at 4p15.32 and the BNC2 (P=4.49×10−10) at 9p22.2 for systolic BP, GGNBP1 (P=1.18×10−8) and LINC00336 (P=1.36×10−8) at 6p21 for diastolic BP, DAB1 (P=1.05×10−13) at 1p32.2 and MIR4466 (P=5.34×10−8) at 6q25.3 for pulse pressure. BNC2 (P=3.57×10−8) gene was also significant for mean arterial pressure. Conclusions We identified 2 novel BP loci and 6 genes through the examination of SNP- and gene-based interactions with potassium.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome-Wide Gene–Potassium Interaction Analyses on Blood Pressure

Chen

et al. 2017

Circ Cardiovasc Genet

View full text Add to dashboard Cite

show abstract

“…In the GWAS-meta-analysis of the European population, genetic loci such as the one on chr 16 (including the uromodulin [ UMOD ] gene), or those on chr 10 (including cadherin 23 [ CDH23 ] gene) and on chr 7 (including solute carrier family 22, member 2 [ SLC22A2 ] and polypeptide Nacetylgalactosaminyltransferase-like protein 5 [ GALNTL5 ] gene) were shown to be significantly associated with renal functions [1, 20, 35-38]. In the present GWAS in Japanese population, these loci were not found to be genome-wide significant, suggesting the possibility that specific genetic mechanisms exist between the races.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Renal Function Traits: Results from the Japan Multi-Institutional Collaborative Cohort Study

et al. 2018

View full text Add to dashboard Cite

Background: Chronic kidney disease (CKD) is a rapidly growing, worldwide public health problem. Recent advances in genome-wide-association studies (GWAS) revealed several genetic loci associated with renal function traits worldwide. Methods: We investigated the association of genetic factors with the levels of serum creatinine (SCr) and the estimated glomerular filtration rate (eGFR) in Japanese population-based cohorts analyzing the GWAS imputed data with 11,221 subjects and 12,617,569 variants, and replicated the findings with the 148,829 hospital-based Japanese subjects. Results: In the discovery phase, 28 variants within 4 loci (chromosome [chr] 2 with 8 variants including rs3770636 in the LDL receptor related protein 2 gene locus, on chr 5 with 2 variants including rs270184, chr 17 with 15 variants including rs3785837 in the BCAS3 gene locus, and chr 18 with 3 variants including rs74183647 in the nuclear factor of activated T-cells 1 gene locus) reached the suggestive level of p < 1 × 10^–6 in association with eGFR and SCr, and 2 variants on chr 4 (including rs78351985 in the microsomal triglyceride transfer protein gene locus) fulfilled the suggestive level in association with the risk of CKD. In the replication phase, 25 variants within 3 loci (chr 2 with 7 variants, chr 17 with 15 variants and chr 18 with 3 variants) in association with eGFR and SCr, and 2 variants on chr 4 associated with the risk of CKD became nominally statistically significant after Bonferroni correction, among which 15 variants on chr 17 and 3 variants on chr 18 reached genome-wide significance of p < 5 × 10^–8 in the combined study meta-analysis. The associations of the loci on chr 2 and 18 with eGFR and SCr as well as that on chr 4 with CKD risk have not been previously reported in the Japanese and East Asian populations. Conclusion: Although the present GWAS of renal function traits included the largest sample of Japanese participants to date, we did not identify novel loci for renal traits. However, we identified the novel associations of the genetic loci on chr 2, 4, and 18 with renal function traits in the Japanese population, suggesting these are transethnic loci. Further investigations of these associations are expected to further validate our findings for the potential establishment of personalized prevention of renal disease in the Japanese and East Asian populations.

show abstract

“…One study by Gorski et al,12 used summary statistics from their GWAS of estimated glomerular filtration rate (eGFR) to create a PRS which was then tested against eGFR in an independent cohort of 1017 individuals. By doing so, PRSs may be more clinically relevant than looking at common genetic variants independently.…”

Section: Introductionmentioning

confidence: 99%

The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population

Genomics

2019

American Journal of Transplantation

Self Cite

View full text Add to dashboard Cite

Genetic variation across the human leukocyte antigen loci is known to influence renal‐transplant outcome. However, the impact of genetic variation beyond the human leukocyte antigen loci is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with posttransplant eGFR at different time‐points, out to 5 years posttransplantation. We conducted GWAS meta‐analyses across 10 844 donors and recipients from five European ancestry cohorts. We also analyzed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with nontransplant eGFR, on posttransplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1‐year posttransplant. Thirty‐two percent of the variability in eGFR at 1‐year posttransplant was explained by our model containing clinical covariates (including weights for death/graft‐failure), principal components and combined donor‐recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFR posttransplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a posttransplant context. Despite PRS being a significant predictor of eGFR posttransplant, the effect size of common genetic factors is limited compared to clinical variables.

show abstract

1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function

Cited by 100 publications

References 53 publications

Genome-Wide Gene–Potassium Interaction Analyses on Blood Pressure

Genome-Wide Gene–Potassium Interaction Analyses on Blood Pressure

Genome-Wide Association Study of Renal Function Traits: Results from the Japan Multi-Institutional Collaborative Cohort Study

The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population

Contact Info

Product

Resources

About