Genome-wide association study identifies variants in casein kinase II (CSNK2A2) to be associated with leukocyte telomere length in a Punjabi Sikh diabetic cohort
| Autor: | Colin P.N. Dinney, Sharon A. Savage, Peter Kraft, Sarju Ralhan, Massimo Mangino, Marvin D. Peyton, Megan R. Lerner, Patrick Dib, Gurpreet Singh Wander, Narinder K. Mehra, Jennifer Prescott, Jacqueline M. Lane, Praveen Natt, Veryan Codd, Dharambir K. Sanghera, Jackie A. Cooper, Jian Gu, Daniel J. Brackett, Tim D. Spector, Lisa Mirabello, Richa Saxena, Xifeng Wu, Andrew Bjonnes, Immaculata De Vivo, Nilesh J. Samani, Yuanqing Ye, Klelia D. Salpea, Donald Stowell, Cécilia Maubaret, Ka Wah Li, Steve E. Humphries, David J. Hunter |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Telomere Pathway Population India Locus (genetics) Genome-wide association study Disease Biology Polymorphism Single Nucleotide Article Cohort Studies Young Adult Asian People Genetics Leukocytes Humans Genetic Predisposition to Disease Phosphorylation education Casein Kinase II Genotyping Allele frequency Genetics (clinical) Aged education.field_of_study Genetic Variation Middle Aged Telomere Religion Diabetes Mellitus Type 2 Female Cardiology and Cardiovascular Medicine Genome-Wide Association Study |
| Zdroj: | Circulation. Cardiovascular genetics. 7(3) |
| ISSN: | 1942-3268 |
| Popis: | 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. 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 –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 –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 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. |
| Databáze: | OpenAIRE |
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