Publication

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

Gorski, M., Van der Most, P. J., Teumer, A., Chu, A. Y., Li, M., Mijatovic, V., Nolte, I. M., Cocca, M., Taliun, D., Gomez, F., Li, Y., Tayo, B., Tin, A., Feitosa, M. F., Aspelund, T., Attia, J., Biffar, R., Bochud, M., Boerwinkle, E., Borecki, I., Bottinger, E. P., Chen, M-H., Chouraki, V., Ciullo, M., Coresh, J., Cornelis, M. C., Curhan, G. C., d'Adamo, A. P., Dehghan, A., Dengler, L., Ding, J., Eiriksdottir, G., Endlich, K., Enroth, S., Esko, T., Franco, O. H., Gasparini, P., Gieger, C., Girotto, G., Gottesman, O., Gudnason, V., Gyllensten, U., Hancock, S. J., Harris, T. B., Helmer, C., Hoellerer, S., Hofer, E., Hofman, A., Holliday, E. G., Homuth, G., Hu, F. B., Huth, C., Hutri-Kahonen, N., Hwang, S-J., Imboden, M., Johansson, A., Kahonen, M., Koenig, W., Kraemer, H., Kramer, B. K., Kumar, A., Kutalik, Z., Lambert, J-C., Launer, L. J., Lehtimaki, T., de Borst, M., Navis, G., Swertz, M., Liu, Y., Lohman, K., Loos, R. J. F., Lu, Y., Lyytikainen, L-P., McEvoy, M. A., Meisinger, C., Meitinger, T., Metspalu, A., Metzger, M., Mihailov, E., Mitchell, P., Nauck, M., Oldehinkel, A. J., Olden, M., Penninx, B. W. J. H., Pistis, G., Pramstaller, P. P., Probst-Hensch, N., Raitakari, O. T., Rettig, R., Ridker, P. M., Rivadeneira, F., Robino, A., Rosas, S. E., Ruderfer, D., Ruggiero, D., Saba, Y., Sala, C., Schmidt, H., Schmidt, R., Scott, R. J., Sedaghat, S., Smith, A. V., Sorice, R., Stengel, B., Stracke, S., Strauch, K., Toniolo, D., Uitterlinden, A. G., Ulivi, S., Viikari, J. S., Voelker, U., Vollenweider, P., Voelzke, H., Vuckovic, D., Waldenberger, M., Wang, J. J., Yang, Q., Chasman, D. I., Tromp, G., Snieder, H., Heid, I. M., Fox, C. S., Koettgen, A., Pattaro, C., Boeger, C. A. & Fuchsberger, C., 28-Apr-2017, In : Scientific Reports. 7, 10 p., 45040.

Research output: Contribution to journalArticleAcademicpeer-review

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

HapMap imputed genome-wide association studies (GWAS) have revealed > 50 loci at which common variants with minor allele frequency > 5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value <5 x 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR <0.05) genes and 127 significantly (FDR <0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until wholegenome sequencing becomes feasible in large samples.

Original languageEnglish
Article number45040
Number of pages10
JournalScientific Reports
Volume7
Publication statusPublished - 28-Apr-2017

    Keywords

  • GLOMERULAR-FILTRATION-RATE, COMMUNITY-BASED POPULATION, WIDE ASSOCIATION, SERUM CREATININE, GENOTYPE IMPUTATION, LINKAGE ANALYSIS, DISEASE, VARIANTS, INTEGRATION, HERITABILITY

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