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Abstract
Objective To examine polygenic inheritance of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of subjective cognitive complaints and slow gait.
Methods We analyzed 4,915 individuals, age 65 years and above, with European ancestry (mean age 75.0 ± 6.8 years, 56.6% women) in the Health and Retirement Study. Polygenic scores (PGS) were calculated as weighted sums of the effect of single nucleotide polymorphisms, with effect sizes derived from genome-wide association studies. The association between PGSs of 9 phenotypes (general cognition, body mass index [BMI], mean arterial pressure, education, Alzheimer disease [AD], neuroticism, well-being, waist circumference, and depressive symptoms) and MCR as well as its key components (cognitive complaints and slow gait) were examined by logistic regression, adjusting for age, sex, education, and genetic ancestry, and reported as odds ratios (ORs) with 95% confidence intervals (CIs).
Results There were 260 prevalent MCR cases, 529 with slow gait, and 1,928 with subjective cognitive complaints. Higher PGSs for BMI (OR 1.22, 95% CI 1.07–1.39) and waist circumference (OR 1.23, 95% CI 1.07–1.40) were associated with MCR, and PGS of AD showed a suggestive association (OR 1.16, 95% CI 1.02–1.32). Higher PGS for neuroticism (OR 1.10, 95% CI 1.03–1.18) was associated with cognitive complaints, whereas higher well-being PGS (OR 0.92, 95% CI 0.87–0.98) was protective. PGS for BMI (OR 1.16, 95% CI 1.06–1.28), waist circumference (OR 1.19, 95% CI 1.08–1.31), and AD (OR 1.13, 95% CI 1.03–1.24) was associated with slow gait.
Conclusion Obesity-related genetic traits increase risk of MCR syndrome; further investigation is required to identify potential therapeutic targets.
Glossary
- AD=
- Alzheimer disease;
- BMI=
- body mass index;
- CI=
- confidence interval;
- FDR=
- false discovery rate;
- GWAS=
- genome-wide association studies;
- HRS=
- Health and Retirement Study;
- LD=
- linkage disequilibrium;
- MCI=
- mild cognitive impairment;
- MCR=
- motoric cognitive risk;
- OR=
- odds ratio;
- PCA=
- principal components analysis;
- PGS=
- polygenic score;
- SNP=
- single nucleotide polymorphism
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received August 17, 2018.
- Accepted in final form November 21, 2018.
- © 2019 American Academy of Neurology
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