Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

Kato, N. et al. (2015) Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. Nature Genetics, 47(11), pp. 1282-1293. (doi: 10.1038/ng.3405) (PMID:26390057) (PMCID:PMC4719169)

Abstract

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Young, Dr Robin and Stott J, Professor David
• Authors: Kato, N., Loh, M., Takeuchi, F., Verweij, N., Wang, X., Zhang, W., Kelly, T. N., Saleheen, D., Lehne, B., Leach, I. M., Drong, A. W., Abbott, J., Wahl, S., Tan, S.-T., Scott, W. R., Campanella, G., Chadeau-Hyam, M., Afzal, U., Ahluwalia, T. S., Bonder, M. J., Chen, P., Dehghan, A., Edwards, T. L., Esko, T., Go, M. J., Harris, S. E., Hartiala, J., Kasela, S., Kasturiratne, A., Khor, C.-C., Kleber, M. E., Li, H., Mok, Z. Y., Nakatochi, M., Sapari, N. S., Saxena, R., Stewart, A. F.R., Stolk, L., Tabara, Y., Teh, A. L., Wu, Y., Wu, J.-Y., Zhang, Y., Aits, I., Da Silva Couto Alves, A., Das, S., Dorajoo, R., Hopewell, J. C., Kim, Y. K., Koivula, R. W., Luan, J.'a., Lyytikäinen, L.-P., Nguyen, Q. N., Pereira, M. A., Postmus, I., Raitakari, O. T., Bryan, M. S., Scott, R. A., Sorice, R., Tragante, V., Traglia, M., White, J., Yamamoto, K., Zhang, Y., Adair, L. S., Ahmed, A., Akiyama, K., Asif, R., Aung, T., Barroso, I., Bjonnes, A., Braun, T. R., Cai, H., Chang, L.-C., Chen, C.-H., Cheng, C.-Y., Chong, Y.-S., Collins, R., Courtney, R., Davies, G., Delgado, G., Do, L. D., Doevendans, P. A., Gansevoort, R. T., Gao, Y.-T., Grammer, T. B., Grarup, N., Grewal, J., Gu, D., Wander, G. S., Hartikainen, A.-L., Hazen, S. L., He, J., Heng, C.-K., Hixson, J. E., Hofman, A., Hsu, C., Huang, W., Husemoen, L. L.N., Hwang, J.-Y., Ichihara, S., Igase, M., Isono, M., Justesen, J. M., Katsuya, T., Kibriya, M. G., Kim, Y. J., Kishimoto, M., Koh, W.-P., Kohara, K., Kumari, M., Kwek, K., Lee, N. R., Lee, J., Liao, J., Lieb, W., Liewald, D. C.M., Matsubara, T., Matsushita, Y., Meitinger, T., Mihailov, E., Milani, L., Mills, R., Mononen, N., Müller-Nurasyid, M., Nabika, T., Nakashima, E., Ng, H. K., Nikus, K., Nutile, T., Ohkubo, T., Ohnaka, K., Parish, S., Paternoster, L., Peng, H., Peters, A., Pham, S. T., Pinidiyapathirage, M. J., Rahman, M., Rakugi, H., Rolandsson, O., Rozario, M. A., Ruggiero, D., Sala, C. F., Sarju, R., Shimokawa, K., Snieder, H., Sparsø, T., Spiering, W., Starr, J. M., Stott, D. J., Stram, D. O., Sugiyama, T., Szymczak, S., Tang, W. H. W., Tong, L., Trompet, S., Turjanmaa, V., Ueshima, H., Uitterlinden, A. G., Umemura, S., Vaarasmaki, M., van Dam, R. M., van Gilst, W. H., van Veldhuisen, D. J., Viikari, J. S., Waldenberger, M., Wang, Y., Wang, A., Wilson, R., Wong, T.-Y., Xiang, Y.-B., Yamaguchi, S., Ye, X., Young, R. D., Young, T. L., Yuan, J.-M., Zhou, X., Asselbergs, F. W., Ciullo, M., Clarke, R., Deloukas, P., Franke, A., Franks, P. W., Franks, S., Friedlander, Y., Gross, M. D., Guo, Z., Hansen, T., Jarvelin, M.-R., Jørgensen, T., Jukema, J. W., Kähönen, M., Kajio, H., Kivimaki, M., Lee, J.-Y., Lehtimäki, T., Linneberg, A., Miki, T., Pedersen, O., Samani, N. J., Sørensen, T. I.A., Takayanagi, R., Toniolo, D., Ahsan, H., Allayee, H., Chen, Y.-T., Danesh, J., Deary, I. J., Franco, O. H., Franke, L., Heijman, B. T., Holbrook, J. D., Isaacs, A., Kim, B.-J., Lin, X., Liu, J., März, W., Metspalu, A., Mohlke, K. L., Sanghera, D. K., Shu, X.-O., van Meurs, J. B.J., Vithana, E., Wickremasinghe, A. R., Wijmenga, C., Wolffenbuttel, B. H.W., Yokota, M., Zheng, W., Zhu, D., Vineis, P., Kyrtopoulos, S. A., Kleinjans, J. C.S., McCarthy, M. I., Soong, R., Gieger, C., Scott, J., Teo, Y.-Y., He, J., Elliott, P., Tai, E. S., van der Harst, P., Kooner, J. S., and Chambers, J. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Nature Genetics
• Publisher: Nature Publishing Group
• ISSN: 1061-4036
• ISSN (Online): 1546-1718