Date: December 2022.
Source: Nature Communications, 13, 7832.
Abstract: 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.

Article: Combining genome-wide association studies highlight novel loci involved in human facial variation.
Authors: Ziyi Xiong, Xingjian Gao, Yan Chen, Zhanying Feng, Siyu Pan, Haojie Lu, Andre G Uitterlinden, Tamar Nijsten, Arfan Ikram, Fernando Rivadeneira, Mohsen Ghanbari, Yong Wang, Manfred Kayser, and Fan Liu. Department of Genetic Identification, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.