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Genomics02:02

Genomics

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Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
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Prediction of Episodic Memory With Multiomics Scores.

Anni L K Malmberg1, Matti Pirinen2,3,4, Johannes Kettunen5,6

  • 1Department of Psychology, University of Helsinki, Helsinki, Finland.

Biological Psychiatry Global Open Science
|October 28, 2025
PubMed
Summary

Genomic risk scores predict episodic memory in adults, but not in children. These polygenic risk scores (PRS) add predictive value beyond traditional risk factors for cognitive aging and dementia risk.

Keywords:
Episodic memoryGenome-wide association analysisMetabolome-wide association analysisMultiomicsNeurocognitionPrediction

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Area of Science:

  • Neuroscience
  • Genetics
  • Gerontology

Background:

  • Episodic memory (EM) is crucial for cognitive aging and a dementia endophenotype.
  • Understanding EM's genetic underpinnings is vital for predicting cognitive decline.
  • Identifying reliable predictors of EM can aid in early dementia risk assessment.

Purpose of the Study:

  • To develop and validate polygenic risk scores (PRS) and metabolic risk scores (MRS) for predicting episodic memory (EM) in adults.
  • To assess the incremental predictive value of PRS and MRS beyond established risk factors (CAIDE score).
  • To evaluate the generalizability of adult-derived PRS in pediatric cohorts.

Main Methods:

  • Genome- and metabolome-wide analyses (LASSO) were used to create LASSO-PRS and MRS in older adults (n=897).
  • An external meta-analysis (N=29,785) generated another PRS (GWAMA-PRS) using PRS-CS.
  • Predictive performance was assessed by incremental R-squared in independent adult cohorts (n=104) and validated in pediatric cohorts (n=309, n=443).

Main Results:

  • Polygenic risk scores (LASSO-PRS and GWAMA-PRS) significantly predicted EM in adults, increasing predictive R-squared by 4.5-5.6 pp beyond the CAIDE score.
  • Combined PRS and MRS (LASSO-PRS + MRS) showed the highest incremental prediction (7.8 pp).
  • Adult-derived PRS did not predict EM in pediatric cohorts (ages ~8.6 and ~11.9 years).

Conclusions:

  • Genomic information, specifically PRS, enhances EM prediction in adults beyond epidemiological factors.
  • Metabolomic risk scores (MRS) did not add significant predictive value for EM in adults.
  • Adult-derived PRS are not predictive of EM in children, suggesting age-specific genetic influences.