Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.

• Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands--yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15 × 10(-36)), SULT2A1 (rs2637125; p =  2.61 × 10(-19)), ARPC1A (rs740160; p =  1.56 × 10(-16)), TRIM4 (rs17277546; p =  4.50 × 10(-11)), BMF (rs7181230; p = 5.44 × 10(-11)), HHEX (rs2497306; p =  4.64 × 10(-9)), BCL2L11 (rs6738028; p = 1.72 × 10(-8)), and CYP2C9 (rs2185570; p = 2.29 × 10(-8)). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

Actin-Related Protein 2-3 Complex

genetics

metabolism

Adaptor Proteins

Signal Transducing

genetics

metabolism

Adult

Aged

Aging

blood

genetics

Apoptosis Regulatory Proteins

genetics

metabolism

Aryl Hydrocarbon Hydroxylases

genetics

metabolism

Dehydroepiandrosterone Sulfate

blood

European Continental Ancestry Group

genetics

Female

Gene Expression

Genome-Wide Association Study

Homeodomain Proteins

genetics

metabolism

Humans

Kruppel-Like Transcription Factors

genetics

metabolism

Linkage Disequilibrium

Liver

metabolism

Male

Membrane Proteins

genetics

metabolism

Middle Aged

Polymorphism

Single Nucleotide

Proto-Oncogene Proteins

genetics

metabolism

Sulfotransferases

genetics

metabolism

Transcription Factors

genetics

metabolism

Young Adult

Publication and Content Type

ref (subject category)

art (subject category)