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Combining genome-wide association studies highlight novel loci involved in human facial variation.
Xiong, Ziyi; Gao, Xingjian; Chen, Yan; Feng, Zhanying; Pan, Siyu; Lu, Haojie; Uitterlinden, Andre G; Nijsten, Tamar; Ikram, Arfan; Rivadeneira, Fernando; Ghanbari, Mohsen; Wang, Yong; Kayser, Manfred; Liu, Fan.
Afiliación
  • Xiong Z; Department of Genetic Identification, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • Gao X; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • Chen Y; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
  • Feng Z; National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing, Jiangsu, China.
  • Pan S; Department of Genetic Identification, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • Lu H; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
  • Uitterlinden AG; CEMS, NCMIS, HCMS, MDIS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China.
  • Nijsten T; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
  • Ikram A; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • Rivadeneira F; Department of Internal Medicine, 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; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • Kayser M; Department of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • Liu F; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Nat Commun ; 13(1): 7832, 2022 12 20.
Article en En | MEDLINE | ID: mdl-36539420
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo de Nucleótido Simple / Estudio de Asociación del Genoma Completo Tipo de estudio: Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo de Nucleótido Simple / Estudio de Asociación del Genoma Completo Tipo de estudio: Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido