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Genetic and non-genetic factors associated with the phenotype of exceptional longevity & normal cognition.

Publication ,  Journal Article
Han, B; Chen, H; Yao, Y; Liu, X; Nie, C; Min, J; Zeng, Y; Lutz, MW
Published in: Sci Rep
November 5, 2020

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 [Formula: see text] 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 [Formula: see text] 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.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

November 5, 2020

Volume

10

Issue

1

Start / End Page

19140

Location

England

Related Subject Headings

  • Ryanodine Receptor Calcium Release Channel
  • Repressor Proteins
  • Receptors, Kainic Acid
  • Prohibitins
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Male
  • Longevity
  • Humans
  • GluK2 Kainate Receptor
 

Citation

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Han, B., Chen, H., Yao, Y., Liu, X., Nie, C., Min, J., … Lutz, M. W. (2020). Genetic and non-genetic factors associated with the phenotype of exceptional longevity & normal cognition. Sci Rep, 10(1), 19140. https://doi.org/10.1038/s41598-020-75446-2
Han, Bin, Huashuai Chen, Yao Yao, Xiaomin Liu, Chao Nie, Junxia Min, Yi Zeng, and Michael W. Lutz. “Genetic and non-genetic factors associated with the phenotype of exceptional longevity & normal cognition.Sci Rep 10, no. 1 (November 5, 2020): 19140. https://doi.org/10.1038/s41598-020-75446-2.
Han B, Chen H, Yao Y, Liu X, Nie C, Min J, et al. Genetic and non-genetic factors associated with the phenotype of exceptional longevity & normal cognition. Sci Rep. 2020 Nov 5;10(1):19140.
Han, Bin, et al. “Genetic and non-genetic factors associated with the phenotype of exceptional longevity & normal cognition.Sci Rep, vol. 10, no. 1, Nov. 2020, p. 19140. Pubmed, doi:10.1038/s41598-020-75446-2.
Han B, Chen H, Yao Y, Liu X, Nie C, Min J, Zeng Y, Lutz MW. Genetic and non-genetic factors associated with the phenotype of exceptional longevity & normal cognition. Sci Rep. 2020 Nov 5;10(1):19140.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

November 5, 2020

Volume

10

Issue

1

Start / End Page

19140

Location

England

Related Subject Headings

  • Ryanodine Receptor Calcium Release Channel
  • Repressor Proteins
  • Receptors, Kainic Acid
  • Prohibitins
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Male
  • Longevity
  • Humans
  • GluK2 Kainate Receptor