Heritability and genetic association analysis of two cognition phenotypes in white European adults

Publication type

Conference Paper

Author

Delilah Zabaneh

Publication date

Summary

This study examined the genetic contribution to individual differences
of prospective memory and verbal fluency cognition traits in
approximately 5800 phenotyped unrelated adults from the England
Longitudinal Study of Ageing (ELSA). The heritability of the cognitive
traits in unrelated individuals was estimated using the Illumina
HumanOmni2.5 array. A genome-wide association analysis was also carried
out using these data. The estimated heritability following adjustment
for age and gender for memory was h2= 0.17 (0.07) and fluency: h2= 0.38
(0.07). Genome-wide assessment revealed significant evidence of
association with memory for two SNPs: rs77287008 and rs9622280 on
chromosome 22, located near the RBFOX2 (RNA Binding Protein, Fox-1
Homolog), p< 4× 10-8. For verbal fluency, one intergenic SNP rs952684
near IMPAD1 (Inositol Monophosphatase Domain Containing 1) with p <
7 × 10-8 showed suggestive evidence of association. Functional
bioinformatics annotation analysis implies that SNP rs77287008 in the
RBFOX2 region has a downstream, non-protein-coding effect indicated by a
PHRED CADD score (C-score) = 15.0, denoting a pathogenic/deleterious
effect. Significant heritabilities for both traits suggest a role for
genetic contributors to memory and verbal fluency, and in the case of
memory, this is supported by the identification of genetic association
signals in a functionally plausible candidate. To replicate these
findings, data will be meta-analysed with three additional studies
including Understanding Society, resulting in approximately 20000
participants. Additionally, cohorts with cognition phenotypes are
available to replicate the most significant SNPs from an extra 7500
samples from studies that have been genotyped using the Illumina
CardioMetabochip array.

Subjects

Medicine, Science And Technology, Health, Biology and Genetics

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