Unknown

Dataset Information

0

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


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.

SUBMITTER: Xiong Z 

PROVIDER: S-EPMC9767941 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Xiong Ziyi Z   Gao Xingjian X   Chen Yan Y   Feng Zhanying Z   Pan Siyu S   Lu Haojie H   Uitterlinden Andre G AG   Nijsten Tamar T   Ikram Arfan A   Rivadeneira Fernando F   Ghanbari Mohsen M   Wang Yong Y   Kayser Manfred M   Liu Fan F  

Nature communications 20221220 1


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 comb  ...[more]

Similar Datasets

| S-EPMC5886212 | biostudies-literature
| S-EPMC6008943 | biostudies-literature
| S-EPMC10918883 | biostudies-literature
| S-EPMC5120758 | biostudies-literature
| S-EPMC4643645 | biostudies-literature
| S-EPMC4999139 | biostudies-literature
| S-EPMC4214417 | biostudies-literature
| S-EPMC3731230 | biostudies-literature
| S-EPMC3395392 | biostudies-literature
| S-EPMC11313457 | biostudies-literature