Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology.
Am J Hum Genet
; 105(1): 15-28, 2019 07 03.
Article
en En
| MEDLINE
| ID: mdl-31178129
ABSTRACT
Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tejido Adiposo
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Predisposición Genética a la Enfermedad
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Polimorfismo de Nucleótido Simple
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Adiponectina
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Exoma
/
Lípidos
/
Obesidad
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Hum Genet
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos