title: ADRB2, brain white matter integrity and cognitive ageing in the Lothian Birth Cohort 1936.
abstract: The non-synonymous mutations arg16gly (rs1042713) and gln27glu (rs1042714) in the adrenergic β-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.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK. D.Lyall-2@sms.ed.ac.uk
authors.forename: Donald M
authors.initials: DM
authors.lastname: Lyall
authors.forename: Lorna M
authors.initials: LM
authors.lastname: Lopez
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bastin
authors.forename: Susana Muñoz
authors.initials: SM
authors.lastname: Maniega
authors.forename: Lars
authors.initials: L
authors.lastname: Penke
authors.forename: Maria del C
authors.initials: Mdel C
authors.lastname: Valdés Hernández
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Royle
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000368:Aged; D000375:Aging; D000483:Alleles; D001921:Brain / Q000473:pathology*; D003071:Cognition; D003072:Cognition Disorders / Q000473:pathology; D015331:Cohort Studies; D038524:Diffusion Magnetic Resonance Imaging; D005189:False Positive Reactions; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D010641:Phenotype; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012606:Scotland
chemical_list: C553443:ADRB2 protein, human; D018343:Receptors, Adrenergic, beta-2