作者
Marta Guindo-Martínez, Ramon Amela, Silvia Bonàs-Guarch, Montserrat Puiggròs, Cecilia Salvoro, Irene Miguel-Escalada, Caitlin E Carey, Joanne B Cole, Sina Rüeger, Elizabeth Atkinson, Aaron Leong, Friman Sanchez, Cristian Ramon-Cortes, Jorge Ejarque, Duncan S Palmer, Mitja Kurki, FinnGen Consortium, Krishna Aragam, Jose C Florez, Rosa M Badia, Josep M Mercader, David Torrents
发表日期
2021/4/23
期刊
Nature communications
卷号
12
期号
1
页码范围
2436
出版商
Nature Publishing Group UK
简介
Genome-wide association studies (GWAS) are not fully comprehensive, as current strategies typically test only the additive model, exclude the X chromosome, and use only one reference panel for genotype imputation. We implement an extensive GWAS strategy, GUIDANCE, which improves genotype imputation by using multiple reference panels and includes the analysis of the X chromosome and non-additive models to test for association. We apply this methodology to 62,281 subjects across 22 age-related diseases and identify 94 genome-wide associated loci, including 26 previously unreported. Moreover, we observe that 27.7% of the 94 loci are missed if we use standard imputation strategies with a single reference panel, such as HRC, and only test the additive model. Among the new findings, we identify three novel low-frequency recessive variants with odds ratios larger than 4, which need at least a three …
引用总数
2020202120222023202448172815
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