Diabetic Phenotypes and Late-Life Dementia Risk: A Mechanism-specific Mendelian Randomization Study.
Alzheimer Dis Assoc Disord
; 30(1): 15-20, 2016.
Article
en En
| MEDLINE
| ID: mdl-26650880
ABSTRACT
BACKGROUND:
Mendelian Randomization (MR) studies have reported that type 2 diabetes (T2D) was not associated with Alzheimer disease (AD). We adopted a modified, mechanism-specific MR design to explore this surprising result.METHODS:
Using inverse-variance weighted MR analysis, we evaluated the association between T2D and AD using data from 39 single nucleotide polymorphisms (SNPs) significantly associated with T2D in DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) and the corresponding associations of each SNP with AD risk obtained from the International Genomics of Alzheimer's Project (IGAP, n=17,008 AD cases and n=37,154 controls). We evaluated mechanism-specific genetic subscores, including ß-cell function, insulin sensitivity, and adiposity, and repeated analyses in 8501 Health and Retirement Study participants for replication and model validation.RESULTS:
In IGAP, the overall T2D polygenic score did not predict AD [odds ratio (OR) for the T2D polygenic score=1.01; 95% confidence interval (CI), 0.96, 1.06] but the insulin sensitivity polygenic score predicted higher AD risk (OR=1.17; 95% CI, 1.02, 1.34). In the Health and Retirement Study, polygenic scores were associated with T2D risk; the associations between insulin sensitivity genetic polygenic score and cognitive phenotypes were not statistically significant.CONCLUSIONS:
Evidence from polygenic scores suggests that insulin sensitivity specifically may affect AD risk, more than T2D overall.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Predisposición Genética a la Enfermedad
/
Diabetes Mellitus Tipo 2
/
Enfermedad de Alzheimer
Tipo de estudio:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Alzheimer Dis Assoc Disord
Asunto de la revista:
NEUROLOGIA
/
PSIQUIATRIA
Año:
2016
Tipo del documento:
Article