Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms.
Hum Mol Genet
; 25(10): 2070-2081, 2016 05 15.
Article
en En
| MEDLINE
| ID: mdl-26911676
ABSTRACT
To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Mapeo Cromosómico
/
Predisposición Genética a la Enfermedad
/
Diabetes Mellitus Tipo 2
/
Estudios de Asociación Genética
Tipo de estudio:
Systematic_reviews
Límite:
Female
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Humans
/
Male
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Reino Unido