Genetic analysis of mitochondrial ribosomal proteins and cognitive aging in postmenopausal women

Khyobeni Mozhui, Beverly M. Snively, Stephen R. Rapp, Robert B. Wallace, Robert Williams, Karen Johnson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Genes encoding mitochondrial ribosomal proteins (MRPs) have been linked to aging and longevity in model organisms (i.e., mice, Caenorhabditis elegans). Here we evaluated if the MRPs have conserved effects on aging traits in humans. We utilized data from 4,504 participants of the Women's Health Initiative Memory Study (WHIMS) who had both longitudinal cognitive data and genetic data. Two aging phenotypes were considered: (1) gross lifespan (time to all-cause mortality), and (2) cognitive aging (longitudinal rate of change in modified mini-mental state scores). We tested genetic association with variants in 78 members of the MRP gene family. Genetic association tests were done at the single nucleotide polymorphism (SNP) level, and at gene-set level using two distinct procedures (GATES and MAGMA). We included SNPs in APOE and adjusted the tests for the APOE-e4 allele, a known risk factor for dementia. The strongest association signal is for the known cognitive aging SNP, rs429358, in APOE (p-value = 5 × 10-28 for cognitive aging; p-value = 0.03 for survival). We found no significant association between the MRPs and survival time. For cognitive aging, we detected SNP level association for rs189661478 in MRPL23 (p-value < 9 × 10-6). Furthermore, the gene-set analysis showed modest but significant association between the MRP family and cognitive aging. In conclusion, our results indicate a potential pathway-level association between the MRPs and cognitive aging that is independent of the APOE locus. We however did not detect association between the MRPs and lifespan.

Original languageEnglish (US)
Article number127
JournalFrontiers in Genetics
Volume8
Issue numberSEP
DOIs
StatePublished - Sep 21 2017

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Ribosomal Proteins
Mitochondrial Proteins
Single Nucleotide Polymorphism
Genes
Survival
Caenorhabditis elegans
Women's Health
Cognitive Aging
Dementia
Alleles
Phenotype
Mortality

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

Cite this

Genetic analysis of mitochondrial ribosomal proteins and cognitive aging in postmenopausal women. / Mozhui, Khyobeni; Snively, Beverly M.; Rapp, Stephen R.; Wallace, Robert B.; Williams, Robert; Johnson, Karen.

In: Frontiers in Genetics, Vol. 8, No. SEP, 127, 21.09.2017.

Research output: Contribution to journalArticle

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