Gene Expression Differences between Offspring of Long-Lived Individuals and Controls in Candidate Longevity Regions: Evidence for PAPSS2 as a Longevity Gene

Laura M. Yerges-Armstrong, Sumbul Chai, Jeffery R. O'Connell, Joanne E. Curran, John Blangero, Braxton D. Mitchell, Alan R. Shuldiner, Coleen M. Damcott

    Research output: Contribution to journalArticlepeer-review

    6 Scopus citations

    Abstract

    Although there is compelling evidence for a genetic contribution to longevity, identification of specific genes that robustly associate with longevity has been a challenge. In order to identify longevity-enhancing genes, we measured differential gene expression between offspring of long-lived Amish (older than 90 years; cases, n = 128) and spouses of these offspring (controls, n = 121) and correlated differentially expressed transcripts with locations of longevity-associated variants detected in a prior genome-wide association study (GWAS) of survival to age 90. Expression of one of these transcripts, 3′-phosphoadenosine 5′-phosphosulfate synthase 2 (PAPSS2), was significantly higher in offspring versus controls (4×10-4) and this association was replicated using quantitative real-time polymerase chain reaction. PAPSS2, a sulfation enzyme located on chromosome 10, is ~80kb upstream of the PAPSS2 transcription start site. We found evidence of cis-expression for the originally reported GWAS SNP and PAPSS2. Monogenic conditions linked to PAPSS2 include andrenocortical androgen excess resulting in premature pubarche and skeletal dysplasias, both of which have premature aging features. In summary, these findings provide novel evidence for PAPSS2 as a longevity locus and illustrate the value of harnessing multiple "-omic" approaches to identify longevity candidates.

    Original languageEnglish (US)
    Pages (from-to)1295-1299
    Number of pages5
    JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
    Volume71
    Issue number10
    DOIs
    StatePublished - Oct 1 2016

    Keywords

    • Gene expression
    • Longevity genetics
    • PAPSS2

    ASJC Scopus subject areas

    • Aging
    • Geriatrics and Gerontology

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