Polymorphisms in LMNA and near a SERPINA gene cluster are associated with cognitive function in older people.
A recent genome-wide association (GWA) study of late-onset Alzheimer's disease (LOAD) identified 15 novel single nucleotide polymorphisms (SNPs) independent of ApoE. We hypothesised that variants associated with LOAD are also associated with poor cognitive function in elderly populations. We measured additive associations between the five most strongly associated LOAD SNPs and grouped Mini Mental State Examination (MMSE) scores. Variants were genotyped in respondents (mean age 79 years) from the Oxford Healthy Ageing project (OHAP) and other sites of the MRC Cognitive Function and Ageing Study (MRC-CFAS). In adjusted ordinal logistic models, two variants were associated with poorer cognitive function: rs11622883 (OR=1.14, 95% CI: 1.01-1.28, p=0.040) and rs505058 (OR=1.29, 95% CI: 1.02-1.64, p=0.036). These SNPs are close to a SERPINA gene cluster and within LMNA, respectively. The mechanisms underlying the associations with cognitive impairment and LOAD require further elucidation, but both genes are interesting candidates for involvement in age-related cognitive impairment.
Peninsula Medical School, RD&E Wonford Site, Exeter, UK.
Christie
C
Cluett
Carol
C
Brayne
Robert
R
Clarke
Grimley
G
Evans
Fiona
F
Matthews
David C
DC
Rubinsztein
Felicia
F
Huppert
David J
DJ
Llewellyn
Neil
N
Rice
William
W
Henley
Timothy M
TM
Frayling
Anna
A
Murray
David
D
Melzer
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics; D015984:Causality; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D034904:Lamin Type A / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D005810:Multigene Family / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D015843:Serpins / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology
C494847:LMNA protein, human; D034904:Lamin Type A; D015843:Serpins