Linkage analyses in Caribbean Hispanic families identify novel loci associated with familial late-onset Alzheimer's disease

摘要: 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 causative variants. Methods selected 67 LOAD perform genome-wide scan. Analysis of the linked was repeated using entire sample 282 families. Validated chromosomal were analyzed joint and association. Results identified 26 (HLOD ≥3.6). validated 13 ≥2.5) family sample. The strongest signal at 11q12.3 (rs2232932: HLOD max  = 4.7, P  = 6.6 × 10 −6 ), a locus located ∼2 Mb upstream membrane-spanning 4A gene cluster. additionally 7p14.3 (rs10255835:  = 4.9,  = 1.2 × 10 −5 region harboring genes associated nervous system ( GARS , GHRHR, NEUROD6 ). Discussion Future sequencing efforts should focus on these because they harbor familial mutations.