Combining genome-wide association studies highlight novel loci involved in human facial variation.

Autor: Xiong Z; Department of Genetic Identification, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Gao X; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.; National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing, Jiangsu, China., Chen Y; Department of Genetic Identification, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China., Feng Z; CEMS, NCMIS, HCMS, MDIS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China., Pan S; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China., Lu H; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Uitterlinden AG; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Nijsten T; Department of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Ikram A; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Rivadeneira F; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Ghanbari M; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Wang Y; CEMS, NCMIS, HCMS, MDIS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China., Kayser M; Department of Genetic Identification, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. m.kayser@erasmusmc.nl., Liu F; Department of Genetic Identification, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. f.liu@erasmusmc.nl.; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. f.liu@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Dec 20; Vol. 13 (1), pp. 7832. Date of Electronic Publication: 2022 Dec 20.
DOI: 10.1038/s41467-022-35328-9
Abstrakt: Standard genome-wide association studies (GWASs) rely on analyzing a single trait at a time. However, many human phenotypes are complex and composed by multiple correlated traits. Here we introduce C-GWAS, a method for combining GWAS summary statistics of multiple potentially correlated traits. Extensive computer simulations demonstrated increased statistical power of C-GWAS compared to the minimal p-values of multiple single-trait GWASs (MinGWAS) and the current state-of-the-art method for combining single-trait GWASs (MTAG). Applying C-GWAS to a meta-analysis dataset of 78 single trait facial GWASs from 10,115 Europeans identified 56 study-wide suggestively significant loci with multi-trait effects on facial morphology of which 17 are novel loci. Using data from additional 13,622 European and Asian samples, 46 (82%) loci, including 9 (53%) novel loci, were replicated at nominal significance with consistent allele effects. Functional analyses further strengthen the reliability of our C-GWAS findings. Our study introduces the C-GWAS method and makes it available as computationally efficient open-source R package for widespread future use. Our work also provides insights into the genetic architecture of human facial appearance.
(© 2022. The Author(s).)
Databáze: MEDLINE
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