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ADRB2, brain white matter integrity and cognitive ageing in the Lothian Birth Cohort 1936

Author(s): D. M. Lyall, L. M. Lopez, M. E. Bastin, S. M. Maniega, L. Penke, M. D. V. Hernandez, N. A. Royle, J. M. Starr, D. J. Porteous, J. M. Wardlaw, I. J. Deary

Abstract:
The non-synonymous mutations arg16gly (rs1042713) and gln27glu (rs1042714) in the adrenergic beta-2 receptor gene (ADRB2) have been associated with cognitive function and brain white matter integrity. The current study aimed to replicate these findings and expand them to a broader range of cognitive and brain phenotypes. The sample used is a community-dwelling group of older people, the Lothian Birth Cohort 1936. They had been assessed cognitively at age 11 years, and undertook further cognitive assessments and brain diffusion MRI tractography in older age. The sample size range for cognitive function variables was N = 686-765, and for neuroimaging variables was N = 488-587. Previously-reported findings with these genetic variants did not replicate in this cohort. Novel, nominally significant associations were observed; notably, the integrity of the left arcuate fasciculus mediated the association between rs1042714 and the Digit Symbol Coding test of information processing speed. No significant associations of cognitive and brain phenotypes with ADRB2 variants survived correction for false discovery rate. Previous findings may therefore have been subject to type 1 error. Further study into links between ADRB2, cognitive function and brain white matter integrity is required.

Full version: Available here

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ISBN: 0001-8244
Publication Year: 2013
Periodical: Behavior Genetics
Periodical Number: 1
Volume: 43
Pages: 13-23
Author Address: Lyall, DM Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland Univ Edinburgh, Div Neuroimaging Sci, Brain Res Imaging Ctr, Edinburgh EH4 2XU, Midlothian, Scotland Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland Univ Edinburgh, Western Gen Hosp, Med Genet Sect, Mol Med Ctr, Edinburgh EH4 2XU, Midlothian, Scotland Univ Edinburgh, SINAPSE Collaborat, Dept Neuroimaging Sci, Edinburgh EH4 2XU, Midlothian, Scotland Western Gen Hosp, Geriatr Med Unit, Edinburgh EH4 2XU, Midlothian, Scotland