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http://bura.brunel.ac.uk/handle/2438/22219
Title: | Multi-trait genome-wide association analysis of blood pressure identifies 45 additional loci |
Authors: | Cabrera, CP Pazoki, R Giri, A Hellwege, JN Evangelou, E Ramirez, J Wain, LV Tzoulaki, I Edwards, TL Elliott, P Munroe, PB Barnes, MR Caulfield, MJ Warren, HR |
Keywords: | Science & Technology;Life Sciences & Biomedicine;Biochemistry & Molecular Biology;Genetics & Heredity |
Issue Date: | 1-Dec-2020 |
Publisher: | Springer Nature |
Citation: | Cabrera, C.P., Pazoki, R., Giri, A. Hellwege, G.N., Evangelou, E., Ramirez, J., Wain, L., Tzoulaki, I., Edwards, T.L., Elliott, P., Munroe, P.B., Barnes, M.R., Caulfield, M.J. and Warren, H.R. on behalf of the VA Million Veteran Program and the ICBP working group (2020) 'Multi-trait genome-wide association analysis of blood pressure identifies 45 additional loci', European Journal of Human Genetics, 2020, 28 (Suppl 1), pp. 105 - 105 (1) |
Abstract: | Introduction: Single-trait genome wide association studies (GWAS) have revealed over 1,000 blood pressure (BP) loci. However, these loci only account for less than one third of the BP genetic variation. Multi-trait GWAS is reported to increase discovery power by jointly analysing highly correlated traits. By performing the first large-scale multi-trait BP GWAS, we aimed 1) to compare multi-trait vs single-trait results and 2) identify additional loci. Methods: We apply MTAG to conduct a multi-trait GWAS of systolic BP, diastolic BP and pulse pressure using results from our recent GWAS discovery analysis of ~750k individuals of European ancestry from UK Biobank and the International Consortium of Blood Pressure. To detect additional loci we tested ~7 million imputed genetic variants applying the same combined 1-stage and 2-stage design criteria as in the original GWAS, with replication using MTAG results from the US Million Veteran Program (n~220k). Results: Single-trait GWAS yielded a higher number of significant independent signals genome-wide. Nevertheless, our multi-trait analysis identified 45 new BP loci that were not detected in the equivalent GWAS, of which nine remain novel (based on further BP loci discoveries since 2018). Conclusions: Our multi-trait GWAS discovered additional BP loci. However, our results illustrate that the benefits of MTAG are trait-specific, requiring high pairwise correlation between all pairs of traits, and that more power is gained when MTAG is also used for meta-analysis of traits from different samples. This suggests that future BP genetics discovery projects should focus efforts on larger meta-analyses including new cohorts. |
URI: | https://bura.brunel.ac.uk/handle/2438/22219 |
DOI: | https://doi.org/10.1038/s41431-020-00740-6 |
ISSN: | 1018-4813 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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