The UK10K project identifies rare variants in health and disease

Walter, K. et al. (2015) The UK10K project identifies rare variants in health and disease. Nature, 526(7571), pp. 82-90. (doi: 10.1038/nature14962) (PMID:26367797)

Abstract

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dominiczak, Professor Anna
• Authors: Walter, K., Min, J. L., Huang, J., Crooks, L., Memari, Y., McCarthy, S., Perry, J. R. B., Xu, C., Futema, M., Lawson, D., Iotchkova, V., Schiffels, S., Hendricks, A. E., Danecek, P., Li, R., Floyd, J., Wain, L. V., Barroso, I., Humphries, S. E., Hurles, M. E., Zeggini, E., Barrett, J. C., Plagnol, V., Brent Richards, J., Greenwood, C. M. T., Timpson, N. J., Durbin, R., Soranzo, N., Bala, S., Clapham, P., Coates, G., Cox, T., Daly, A., Danecek, P., Du, Y., Durbin, R., Edkins, S., Ellis, P., Flicek, P., Guo, X., Guo, X., Huang, L., Jackson, D. K., Joyce, C., Keane, T., Kolb-Kokocinski, A., Langford, C., Li, Y., Liang, J., Lin, H., Liu, R., Maslen, J., McCarthy, S., Muddyman, D., Quail, M. A., Stalker, J., Sun, J., Tian, J., Wang, G., Wang, J., Wang, Y., Wong, K., Zhang, P., Barroso, I., Birney, E., Boustred, C., Chen, L., Clement, G., Cocca, M., Danecek, P., Davey Smith, G., Day, I. N. M., Day-Williams, A., Down, T., Dunham, I., Durbin, R., Evans, D. M., Gaunt, T. R., Geihs, M., Greenwood, C. M. T., Hart, D., Hendricks, A. E., Howie, B., Huang, J., Hubbard, T., Hysi, P., Iotchkova, V., Jamshidi, Y., Karczewski, K. J., Kemp, J. P., Lachance, G., Lawson, D., Lek, M., Lopes, M., MacArthur, D. G., Marchini, J., Mangino, M., Mathieson, I., McCarthy, S., Memari, Y., Metrustry, S., Min, J. L., Moayyeri, A., Muddyman, D., Northstone, K., Panoutsopoulou, K., Paternoster, L., Perry, J. R. B., Quaye, L., Brent Richards, J., Ring, S., Ritchie, G. R. S., Schiffels, S., Shihab, H. A., Shin, S.-Y., Small, K. S., Soler Artigas, M., Soranzo, N., Southam, L., Spector, T. D., St Pourcain, B., Surdulescu, G., Tachmazidou, I., Timpson, N. J., Tobin, M. D., Valdes, A. M., Visscher, P. M., Wain, L. V., Walter, K., Ward, K., Wilson, S. G., Wong, K., Yang, J., Zeggini, E., Zhang, F., Zheng, H.-F., Anney, R., Ayub, M., Barrett, J. C., Blackwood, D., Bolton, P. F., Breen, G., Collier, D. A., Craddock, N., Crooks, L., Curran, S., Curtis, D., Durbin, R., Gallagher, L., Geschwind, D., Gurling, H., Holmans, P., Lee, I., Lönnqvist, J., McCarthy, S., McGuffin, P., McIntosh, A. M., McKechanie, A. G., McQuillin, A., Morris, J., Muddyman, D., O'Donovan, M. C., Owen, M. J., Palotie, A., Parr, J. R., Paunio, T., Pietilainen, O., Rehnström, K., Sharp, S. I., Skuse, D., St Clair, D., Suvisaari, J., Walters, J. T. R., Williams, H. J., Barroso, I., Bochukova, E., Bounds, R., Dominiczak, A., Durbin, R., Farooqi, I. S., Hendricks, A. E., Keogh, J., Marenne, G., McCarthy, S., Morris, A., Muddyman, D., O'Rahilly, S., Porteous, D. J., Smith, B. H., Tachmazidou, I., Wheeler, E., Zeggini, E., Al Turki, S., Anderson, C. A., Antony, D., Barroso, I., Beales, P., Bentham, J., Bhattacharya, S., Calissano, M., Carss, K., Chatterjee, K., Cirak, S., Cosgrove, C., Durbin, R., Fitzpatrick, D. R., Floyd, J., Reghan Foley, A., Franklin, C. S., Futema, M., Grozeva, D., Humphries, S. E., Hurles, M. E., McCarthy, S., Mitchison, H. M., Muddyman, D., Muntoni, F., O'Rahilly, S., Onoufriadis, A., Parker, V., Payne, F., Plagnol, V., Lucy Raymond, F., Roberts, N., Savage, D. B., Scambler, P., Schmidts, M., Schoenmakers, N., Semple, R. K., Serra, E., Spasic-Boskovic, O., Stevens, E., van Kogelenberg, M., Vijayarangakannan, P., Walter, K., Williamson, K. A., Wilson, C., Whyte, T., Ciampi, A., Greenwood, C. M. T., Hendricks, A. E., Li, R., Metrustry, S., Oualkacha, K., Tachmazidou, I., Xu, C., Zeggini, E., Bobrow, M., Bolton, P. F., Durbin, R., Fitzpatrick, D. R., Griffin, H., Hurles, M. E., Kaye, J., Kennedy, K., Kent, A., Muddyman, D., Muntoni, F., Lucy Raymond, F., Semple, R. K., Smee, C., Spector, T. D., Timpson, N. J., Charlton, R., Ekong, R., Futema, M., Humphries, S. E., Khawaja, F., Lopes, L. R., Migone, N., Payne, S. J., Plagnol, V., Pollitt, R. C., Povey, S., Ridout, C. K., Robinson, R. L., Scott, R. H., Shaw, A., Syrris, P., Taylor, R., Vandersteen, A. M., Barrett, J. C., Barroso, I., Davey Smith, G., Durbin, R., Farooqi, I. S., Fitzpatrick, D. R., Hurles, M. E., Kaye, J., Kennedy, K., Langford, C., McCarthy, S., Muddyman, D., Owen, M. J., Palotie, A., Brent Richards, J., Soranzo, N., Spector, T. D., Stalker, J., Timpson, N. J., Zeggini, E., Amuzu, A., Pablo Casas, J., Chambers, J. C., Cocca, M., Dedoussis, G., Gambaro, G., Gasparini, P., Gaunt, T. R., Huang, J., Iotchkova, V., Isaacs, A., Johnson, J., Kleber, M. E., Kooner, J. S., Langenberg, C., Luan, J.'a., Malerba, G., März, W., Matchan, A., Min, J. L., Morris, R., Nordestgaard, B. G., Benn, M., Ring, S., Scott, R. A., Soranzo, N., Southam, L., Timpson, N. J., Toniolo, D., Traglia, M., Tybjaerg-Hansen, A., van Duijn, C. M., van Leeuwen, E. M., Varbo, A., Whincup, P., Zaza, G., Zeggini, E., and Zhang, W.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Nature
• Publisher: Nature Publishing Group
• ISSN: 0028-0836
• ISSN (Online): 1476-4687
• Copyright Holders: Copyright © 2015 Macmillan Publishers Limited
• First Published: First published in Nature 526(7571):82-90
• Publisher Policy: Reproduced under a Creative Commons License