Journal article
Genetic Analysis of Mitochondrial Ribosomal Proteins and Cognitive Aging in Postmenopausal Women
Frontiers in genetics, Vol.8, pp.127-127
09/21/2017
DOI: 10.3389/fgene.2017.00127
PMCID: PMC5613226
PMID: 28983317
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
-ε4 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
MRP
s and lifespan.
Details
- Title: Subtitle
- Genetic Analysis of Mitochondrial Ribosomal Proteins and Cognitive Aging in Postmenopausal Women
- Creators
- Khyobeni Mozhui - University of Tennessee Health Science CenterBeverly M. Snively - Wake Forest UniversityStephen R. Rapp - Wake Forest UniversityRobert B. Wallace - University of IowaRobert W. Williams - University of Tennessee Health Science CenterKaren C. Johnson - University of Tennessee Health Science Center
- Resource Type
- Journal article
- Publication Details
- Frontiers in genetics, Vol.8, pp.127-127
- DOI
- 10.3389/fgene.2017.00127
- PMID
- 28983317
- PMCID
- PMC5613226
- NLM abbreviation
- Front Genet
- ISSN
- 1664-8021
- eISSN
- 1664-8021
- Publisher
- Frontiers Media S.A
- Language
- English
- Date published
- 09/21/2017
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984363587402771
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