Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging.

Adult Aged Aged, 80 and over Cohort Studies Diagnostic Imaging Female Genetic Predisposition to Disease / genetics Genotype Heart Diseases / genetics Humans Male Metabolomics Middle Aged Phenotype Precision Medicine / methods Whole Genome Sequencing Young Adult

advanced imaging deep phenotyping genomics metabolomics precision medicine

Journal

Proceedings of the National Academy of Sciences of the United States of America

ISSN: 1091-6490

Titre abrégé: Proc Natl Acad Sci U S A

Pays: United States

ID NLM: 7505876

Informations de publication

Date de publication:
11 02 2020

Historique:

pubmed: 26 1 2020

medline: 12 5 2020

entrez: 26 1 2020

Statut: ppublish

Résumé

Genome sequencing has established clinical utility for rare disease diagnosis. While increasing numbers of individuals have undergone elective genome sequencing, a comprehensive study surveying genome-wide disease-associated genes in adults with deep phenotyping has not been reported. Here we report the results of a 3-y precision medicine study with a goal to integrate whole-genome sequencing with deep phenotyping. A cohort of 1,190 adult participants (402 female [33.8%]; mean age, 54 y [range 20 to 89+]; 70.6% European) had whole-genome sequencing, and were deeply phenotyped using metabolomics, advanced imaging, and clinical laboratory tests in addition to family/medical history. Of 1,190 adults, 206 (17.3%) had at least 1 genetic variant with pathogenic (P) or likely pathogenic (LP) assessment that suggests a predisposition of genetic risk. A multidisciplinary clinical team reviewed all reportable findings for the assessment of genotype and phenotype associations, and 137 (11.5%) had genotype and phenotype associations. A high percentage of genotype and phenotype associations (>75%) was observed for dyslipidemia (

Identifiants

DOI: 10.1073/pnas.1909378117 PMID: 31980526 PMC: PMC7022190

pubmed: 31980526

pii: 1909378117

doi: 10.1073/pnas.1909378117

pmc: PMC7022190

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

3053-3062

Informations de copyright

Déclaration de conflit d'intérêts

Competing interest statement: Y.-C.C.H., H.-C.Y., N.M.S.-A., R.H., L.N., S.D., K.D., P.B., N.H., A.M.K., J.C.V., D.S.K., and C.T.C. are employees of Human Longevity, Inc.

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