TY - JOUR
T1 - The association of genetic variants in interleukin-1 genes with cognition
T2 - Findings from the cardiovascular health study
AU - Benke, K. S.
AU - Carlson, M. C.
AU - Doan, B. Q.
AU - Walston, J. D.
AU - Xue, Q. L.
AU - Reiner, A. P.
AU - Fried, L. P.
AU - Arking, D. E.
AU - Chakravarti, A.
AU - Fallin, M. D.
N1 - Funding Information:
This study was supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number U01 HL080295 from the National, Heart, Lung and Blood Institute , and grant AG15928 from the National Institute on Aging , with additional contribution from the National Institute of Neurological Disorders and Stroke . A full list of principal CHS investigators and institutions can be found at http://www.chs - nhlbi.org/pi.htm . The Johns Hopkins Older Adults Indepedence Center (P30-AG021334) provided funding genotyping and analytic support. We would also like to thank Alexis Rea and Gina Davis for their assistance with the Biotrove genotyping for this project.
PY - 2011/12
Y1 - 2011/12
N2 - The inflammatory cytokine interleukin-1 (IL1) potentially plays a role in cognitive deterioration through pathology due to a dementing disorder or due to an aging process. Study of genetic variants in the IL1 genes has been mostly limited to diseases such as Alzheimer's, however, there may be benefit to studying a continuous measure of cognition. Using data from the Cardiovascular Health Study, we evaluate genetic variation in the genes encoding inflammatory agonists IL1A and IL1B, and the antagonist IL1RN, with repeated measures of global cognition (3MS) and processing speed (DSST), using mixed effects models. We found statistically significant minor allele SNP associations with baseline performance on the 3MS in the IL1RN gene for Caucasians (rs17042917: beta = 0.47, 95%CI = 0.09, 0.85, p = 0.016; rs4251961: beta = - 0.36, 95%CI = - 0.13,-0.60, p = 0.0027; rs931471: beta = 0.39, 95%CI = 0.13, 0.65, p = 0.0032), and the IL1B gene for African Americans (rs1143627: beta = 1.6, 95%CI = 0.48, 2.8; p = 0.006 and rs1143634: beta = 2.09, 95%CI = 0.39, 3.8; p = 0.016). Associations appear to be weaker in a subgroup with higher education level. Upon removing those diagnosed with dementia, effect sizes and statistical significance attenuated. These results provide supporting evidence that genetic variants in IL1 genes may be involved in inflammatory-related lowered cognition, that higher education may modify genetic predisposition, and that these associations may be driven by a dementia process.
AB - The inflammatory cytokine interleukin-1 (IL1) potentially plays a role in cognitive deterioration through pathology due to a dementing disorder or due to an aging process. Study of genetic variants in the IL1 genes has been mostly limited to diseases such as Alzheimer's, however, there may be benefit to studying a continuous measure of cognition. Using data from the Cardiovascular Health Study, we evaluate genetic variation in the genes encoding inflammatory agonists IL1A and IL1B, and the antagonist IL1RN, with repeated measures of global cognition (3MS) and processing speed (DSST), using mixed effects models. We found statistically significant minor allele SNP associations with baseline performance on the 3MS in the IL1RN gene for Caucasians (rs17042917: beta = 0.47, 95%CI = 0.09, 0.85, p = 0.016; rs4251961: beta = - 0.36, 95%CI = - 0.13,-0.60, p = 0.0027; rs931471: beta = 0.39, 95%CI = 0.13, 0.65, p = 0.0032), and the IL1B gene for African Americans (rs1143627: beta = 1.6, 95%CI = 0.48, 2.8; p = 0.006 and rs1143634: beta = 2.09, 95%CI = 0.39, 3.8; p = 0.016). Associations appear to be weaker in a subgroup with higher education level. Upon removing those diagnosed with dementia, effect sizes and statistical significance attenuated. These results provide supporting evidence that genetic variants in IL1 genes may be involved in inflammatory-related lowered cognition, that higher education may modify genetic predisposition, and that these associations may be driven by a dementia process.
KW - Cognition
KW - Genetic epidemiology
KW - Inflammation
KW - Interleukin-1
KW - Longitudinal study
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U2 - 10.1016/j.exger.2011.09.005
DO - 10.1016/j.exger.2011.09.005
M3 - Article
C2 - 21968104
AN - SCOPUS:80855139971
SN - 0531-5565
VL - 46
SP - 1010
EP - 1019
JO - Experimental Gerontology
JF - Experimental Gerontology
IS - 12
ER -