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Human longevity and common variations in the LMNA gene: a meta-analysis
Karen N Conneely1, Brian C Capell, Michael R Erdos
1Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. kconnee@emory.edu
Aging Cell
|February 21, 2012
Summary
Genetic variations in the LMNA gene are linked to longevity. Researchers identified a specific haplotype associated with longer lifespans, suggesting a role for LMNA in human aging processes.
Area of Science:
- Genetics
- Aging Research
- Molecular Biology
Background:
- Mutations in the LMNA gene cause Hutchinson-Gilford progeria syndrome (HGPS), a severe premature aging disorder.
- Emerging evidence suggests LMNA gene products may influence normal cellular senescence and aging.
- Understanding LMNA's role in aging is crucial for insights into longevity and age-related diseases.
Purpose of the Study:
- To investigate the association between LMNA gene variants and human longevity.
- To explore the potential role of LMNA in normal physiological aging processes.
Main Methods:
- Genotyped 16 single nucleotide polymorphisms (SNPs) across the LMNA gene in long-lived individuals (LLI, ≥95 years) and younger controls.
- Haplotype analysis was performed on common nonredundant haplotypes (frequency ≥0.05) to identify associations with longevity.
- Replication studies and meta-analysis were conducted using multiple independent cohorts of LLI and controls.
Main Results:
- A significant association was found between a specific four-SNP haplotype in the LMNA gene and longevity in the initial US Caucasian sample (OR=1.56, P=2.5 × 10(-5)).
- This association was replicated in the New England Centenarian Study (NECS) sample (OR=1.60, P=0.0023) but not in three other independent cohorts.
- A meta-analysis combining all five samples confirmed the significant association of the top haplotype with longevity (OR=1.18, P=7.5 × 10(-4)), with a multiple-testing-adjusted P=0.037.
Conclusions:
- The study suggests that variants within the LMNA gene may contribute to human lifespan.
- The identified haplotype's association with longevity, confirmed through meta-analysis, supports LMNA's role in aging.
- Further research is warranted to elucidate the precise mechanisms by which LMNA influences human longevity.
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