Associations with metabolites in Chinese suggest new metabolic roles in Alzheimer's and Parkinson's diseases.
Hum Mol Genet
; 29(2): 189-201, 2020 01 15.
Article
em En
| MEDLINE
| ID: mdl-31628463
ABSTRACT
Metabolites are small intermediate products of cellular metabolism perturbed in a variety of complex disorders. Identifying genetic markers associated with metabolite concentrations could delineate disease-related metabolic pathways in humans. We tested genetic variants for associations with 136 metabolites in 1954 Chinese from Singapore. At a conservative genome-wide threshold (3.7 × 10-10), we detected 1899 variant-metabolite associations at 16 genetic loci. Three loci (ABCA7, A4GALT, GSTM2) represented novel associations with metabolites, with the strongest association observed between ABCA7 and d181/241 dihexosylceramide. Among 13 replicated loci, we identified six new variants independent of previously reported metabolite or lipid signals. We observed variant-metabolite associations at two loci (ABCA7, CHCHD2) that have been linked to neurodegenerative diseases. At SGPP1 and SPTLC3 loci, genetic variants showed preferential selectivity for sphingolipids with d16 (rather than d18) sphingosine backbone, including sphingosine-1-phosphate (S1P). Our results provide new genetic associations for metabolites and highlight the role of metabolites as intermediate modulators in disease metabolic pathways.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Esfingolipídeos
/
Glicoesfingolipídeos
/
Povo Asiático
/
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
País/Região como assunto:
Asia
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Singapura