Linkage analyses in Caribbean Hispanic families identify novel loci associated with familial late-onset Alzheimer's disease.
Alzheimers Dement
; 11(12): 1397-1406, 2015 Dec.
Article
en En
| MEDLINE
| ID: mdl-26433351
ABSTRACT
INTRODUCTION:
We performed linkage analyses in Caribbean Hispanic families with multiple late-onset Alzheimer's disease (LOAD) cases to identify regions that may contain disease causative variants.METHODS:
We selected 67 LOAD families to perform genome-wide linkage scan. Analysis of the linked regions was repeated using the entire sample of 282 families. Validated chromosomal regions were analyzed using joint linkage and association.RESULTS:
We identified 26 regions linked to LOAD (HLOD ≥3.6). We validated 13 of the regions (HLOD ≥2.5) using the entire family sample. The strongest signal was at 11q12.3 (rs2232932 HLODmax = 4.7, Pjoint = 6.6 × 10(-6)), a locus located â¼2 Mb upstream of the membrane-spanning 4A gene cluster. We additionally identified a locus at 7p14.3 (rs10255835 HLODmax = 4.9, Pjoint = 1.2 × 10(-5)), a region harboring genes associated with the nervous system (GARS, GHRHR, and NEUROD6).DISCUSSION:
Future sequencing efforts should focus on these regions because they may harbor familial LOAD causative mutations.Palabras clave
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Hispánicos o Latinos
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Polimorfismo de Nucleótido Simple
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Enfermedad de Alzheimer
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Ligamiento Genético
Tipo de estudio:
Risk_factors_studies
Límite:
Aged
/
Aged80
/
Female
/
Humans
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Male
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Middle aged
País/Región como asunto:
America do norte
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Caribe
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Puerto rico
/
Republica dominicana
Idioma:
En
Revista:
Alzheimers Dement
Año:
2015
Tipo del documento:
Article