Journal
EUROPEAN JOURNAL OF HUMAN GENETICS
Volume 24, Issue 6, Pages 919-923Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2015.210
Keywords
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Funding
- Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6]
- Scottish Funding Council [HR03006]
- UK Medical Research Council (MRC)
- MRC
- BBSRC
- Chief Scientist Office [CZD/16/6/4] Funding Source: researchfish
- Medical Research Council [MR/K026992/1, MC_PC_U127561128, G0700704] Funding Source: researchfish
- MRC [G0700704, MC_PC_U127561128] Funding Source: UKRI
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The association between APOE genotype and cognitive function suggests a positive role for the e2 allele and a negative role for the e4 allele. Both alleles have relatively low frequencies in the general population; hence, meta-analyses have been based on many small, heterogeneous studies. Here, we report the APOE-cognition associations in the largest single analysis to date. APOE status and cognitive ability were measured in 18 337 participants from the Generation Scotland study between 2006 and 2011. The age range was 18-94 years with a mean of 47 (SD 15). Four cognitive domains were assessed: verbal declarative memory (paragraph recall), processing speed (digit symbol substitution), verbal fluency (phonemic verbal fluency), and vocabulary (Mill Hill synonyms). Linear regression was used to assess the associations between APOE genetic status and cognition. Possession of the e4 allele was associated with lower scores on the measures of memory and processing speed in subjects aged >60. Across all age ranges, the e4 allele was linked to better verbal fluency scores. In younger subjects (<= 60 years) the e4 allele was linked to higher vocabulary scores. There were no associations between the e2 allele and cognitive ability. As seen in previous meta-analyses, the APOE e4 allele is linked to poorer cognitive performance in the domains of memory and processing speed. By contrast, positive associations were seen between the e4 allele and measures of verbal fluency and vocabulary. All associations were relatively small and, in many cases, nominally significant despite the very large sample size.
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