Repeat length variations in polyglutamine disease-associated genes affect body mass index.
Int J Obes (Lond)
; 43(3): 440-449, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30120431
ABSTRACT
BACKGROUND:
The worldwide prevalence of obesity, a major risk factor for numerous debilitating chronic disorders, is increasing rapidly. Although a substantial amount of the variation in body mass index (BMI) is estimated to be heritable, the largest meta-analysis of genome-wide association studies (GWAS) to date explained only ~2.7% of the variation. To tackle this 'missing heritability' problem of obesity, here we focused on the contribution of DNA repeat length polymorphisms which are not detectable by GWAS. SUBJECTS ANDMETHODS:
We determined the cytosine-adenine-guanine (CAG) repeat length in the nine known polyglutamine disease-associated genes (ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, HTT, ATN1 and AR) in two large cohorts consisting of 12,457 individuals and analyzed their association with BMI, using generalized linear mixed-effect models.RESULTS:
We found a significant association between BMI and the length of CAG repeats in seven polyglutamine disease-associated genes (including ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP and AR). Importantly, these repeat variations could account for 0.75% of the total BMI variation.CONCLUSIONS:
Our findings incriminate repeat polymorphisms as an important novel class of genetic risk factors of obesity and highlight the role of the brain in its pathophysiology.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
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Sequências Repetitivas de Ácido Nucleico
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Índice de Massa Corporal
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Doenças do Sistema Nervoso Central
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Obesidade
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
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:
Int J Obes (Lond)
Assunto da revista:
METABOLISMO
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Holanda