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Genome-wide association study identifies variants in casein kinase II (CSNK2A2) to be associated with leukocyte telomere length in a Punjabi Sikh diabetic cohort.
- Source :
-
Circulation. Cardiovascular genetics [Circ Cardiovasc Genet] 2014 Jun; Vol. 7 (3), pp. 287-95. Date of Electronic Publication: 2014 May 03. - Publication Year :
- 2014
-
Abstract
- Background: Telomere length is a heritable trait, and short telomere length has been associated with multiple chronic diseases. We investigated the relationship of relative leukocyte telomere length with cardiometabolic risk and performed the first genome-wide association study and meta-analysis to identify variants influencing relative telomere length in a population of Sikhs from South Asia.<br />Methods and Results: Our results revealed a significant independent association of shorter relative telomere length with type 2 diabetes mellitus and heart disease. Our discovery genome-wide association study (n=1616) was followed by stage 1 replication of 25 top signals (P<10(-6)) in an additional Sikhs (n=2397). On combined discovery and stage 1 meta-analysis (n= 4013), we identified a novel relative telomere length locus at chromosome 16q21 represented by an intronic variant (rs74019828) in the CSNK2A2 gene (β=-0.38; P=4.5×10(-8)). We further tested 3 top variants by genotyping in UK cardiovascular disease (UKCVD) (whites n=2952) for stage 2. Next, we performed in silico replication of 139 top signals (P<10(-5)) in UK Twin, Nurses Heart Study, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, and MD Anderson Cancer Controls (n=10 033) and joint meta-analysis (n=16 998). The observed signal in CSNK2A2 was confined to South Asians and could not be replicated in whites because of significant difference in allele frequencies (P<0.001). CSNK2A2 phosphorylates telomeric repeat binding factor 1 and plays an important role for regulation of telomere length homoeostasis.<br />Conclusions: By identification of a novel signal in telomere pathway genes, our study provides new molecular insight into the underlying mechanism that may regulate telomere length and its association with human aging and cardiometabolic pathophysiology.<br /> (© 2014 American Heart Association, Inc.)
- Subjects :
- Adult
Aged
Asian People genetics
Casein Kinase II metabolism
Cohort Studies
Diabetes Mellitus, Type 2 genetics
Diabetes Mellitus, Type 2 metabolism
Female
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Humans
India
Leukocytes enzymology
Male
Middle Aged
Phosphorylation
Polymorphism, Single Nucleotide
Religion
Young Adult
Casein Kinase II genetics
Diabetes Mellitus, Type 2 enzymology
Leukocytes metabolism
Telomere metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1942-3268
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Circulation. Cardiovascular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 24795349
- Full Text :
- https://doi.org/10.1161/CIRCGENETICS.113.000412