Genome-wide association studies and polygenic risk score phenome-wide association studies across complex phenotypes in the human phenotype project.
SNPs
Translation to population health
UKBB
biobank
genetics
genome-wide association study
polygenic risk score
Journal
Med (New York, N.Y.)
ISSN: 2666-6340
Titre abrégé: Med
Pays: United States
ID NLM: 101769215
Informations de publication
Date de publication:
21 Dec 2023
21 Dec 2023
Historique:
received:
03
04
2023
revised:
29
09
2023
accepted:
03
12
2023
medline:
2
1
2024
pubmed:
2
1
2024
entrez:
29
12
2023
Statut:
aheadofprint
Résumé
Genome-wide association studies (GWASs) associate phenotypes and genetic variants across a study cohort. GWASs require large-scale cohorts with both phenotype and genetic sequencing data, limiting studied phenotypes. The Human Phenotype Project is a longitudinal study that has measured a wide range of clinical and biomolecular features from a self-assignment cohort over 5 years. The phenotypes collected are quantitative traits, providing higher-resolution insights into the genetics of complex phenotypes. We present the results of GWASs and polygenic risk score phenome-wide association studies with 729 clinical phenotypes and 4,043 molecular features from the Human Phenotype Project. This includes clinical traits that have not been previously associated with genetics, including measures from continuous sleep monitoring, continuous glucose monitoring, liver ultrasound, hormonal status, and fundus imaging. In GWAS of 8,706 individuals, we found significant associations between 169 clinical traits and 1,184 single-nucleotide polymorphisms. We found genes associated with both glycemic control and mental disorders, and we quantify the strength of genetic signals in serum metabolites. In polygenic risk score phenome-wide association studies for clinical traits, we found 16,047 significant associations. The entire set of findings, which we disseminate publicly, provides newfound resolution into the genetic architecture of complex human phenotypes. E.S. is supported by the Minerva foundation with funding from the Federal German Ministry for Education and Research and by the European Research Council and the Israel Science Foundation.
Sections du résumé
BACKGROUND
BACKGROUND
Genome-wide association studies (GWASs) associate phenotypes and genetic variants across a study cohort. GWASs require large-scale cohorts with both phenotype and genetic sequencing data, limiting studied phenotypes. The Human Phenotype Project is a longitudinal study that has measured a wide range of clinical and biomolecular features from a self-assignment cohort over 5 years. The phenotypes collected are quantitative traits, providing higher-resolution insights into the genetics of complex phenotypes.
METHODS
METHODS
We present the results of GWASs and polygenic risk score phenome-wide association studies with 729 clinical phenotypes and 4,043 molecular features from the Human Phenotype Project. This includes clinical traits that have not been previously associated with genetics, including measures from continuous sleep monitoring, continuous glucose monitoring, liver ultrasound, hormonal status, and fundus imaging.
FINDINGS
RESULTS
In GWAS of 8,706 individuals, we found significant associations between 169 clinical traits and 1,184 single-nucleotide polymorphisms. We found genes associated with both glycemic control and mental disorders, and we quantify the strength of genetic signals in serum metabolites. In polygenic risk score phenome-wide association studies for clinical traits, we found 16,047 significant associations.
CONCLUSIONS
CONCLUSIONS
The entire set of findings, which we disseminate publicly, provides newfound resolution into the genetic architecture of complex human phenotypes.
FUNDING
BACKGROUND
E.S. is supported by the Minerva foundation with funding from the Federal German Ministry for Education and Research and by the European Research Council and the Israel Science Foundation.
Identifiants
pubmed: 38157848
pii: S2666-6340(23)00400-2
doi: 10.1016/j.medj.2023.12.001
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests H.R., D.W.-V., T.S., and A.D. are employees of Pheno.AI, Ltd, a biomedical data science company from Tel-Aviv, Israel. A.W., A.K., and E.S. are paid consultants to Pheno.AI, Ltd.