Combining genome-wide association studies highlight novel loci involved in human facial variation.
Nat Commun
; 13(1): 7832, 2022 12 20.
Article
em En
| MEDLINE
| ID: mdl-36539420
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.
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Base de dados:
MEDLINE
Assunto principal:
Polimorfismo de Nucleotídeo Único
/
Estudo de Associação Genômica Ampla
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article