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Genetic and non-genetic factors associated with the phenotype of exceptional longevity & normal cognition
- Source :
- Scientific Reports, Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- In this study, we split 2156 individuals from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) data into two groups, establishing a phenotype of exceptional longevity & normal cognition versus cognitive impairment. We conducted a genome-wide association study (GWAS) to identify significant genetic variants and biological pathways that are associated with cognitive impairment and used these results to construct polygenic risk scores. We elucidated the important and robust factors, both genetic and non-genetic, in predicting the phenotype, using several machine learning models. The GWAS identified 28 significant SNPs at p-value $$< 3 \times 10^{-5}$$ < 3 × 10 - 5 significance level and we pinpointed four genes, ESR1, PHB, RYR3, GRIK2, that are associated with the phenotype though immunological systems, brain function, metabolic pathways, inflammation and diet in the CLHLS cohort. Using both genetic and non-genetic factors, four machine learning models have close prediction results for the phenotype measured in Area Under the Curve: random forest (0.782), XGBoost (0.781), support vector machine with linear kernel (0.780), and $$\ell _2$$ ℓ 2 penalized logistic regression (0.780). The top four important and congruent features in predicting the phenotype identified by these four models are: polygenic risk score, sex, age, and education.
- Subjects :
- Male
0301 basic medicine
Aging
China
media_common.quotation_subject
Longevity
lcsh:Medicine
Genome-wide association study
Biology
Genome informatics
Logistic regression
Genome-wide association studies
Polymorphism, Single Nucleotide
Article
03 medical and health sciences
Cognition
0302 clinical medicine
Receptors, Kainic Acid
Polymorphism (computer science)
GRIK2
Machine learning
Prohibitins
Humans
Genetic Predisposition to Disease
lcsh:Science
Geriatric Assessment
Gene
media_common
Aged, 80 and over
Genetics
Multidisciplinary
Cognitive ageing
lcsh:R
Estrogen Receptor alpha
Ryanodine Receptor Calcium Release Channel
Phenotype
Repressor Proteins
030104 developmental biology
Cohort
biology.protein
lcsh:Q
Female
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....e024762d5b8795423f7a4748e4c26a88