Epigenome-wide association study of leukocyte telomere length.

Author: Lee Y1, Sun D2,3, Ori APS4, Lu AT5, Seeboth A6, Harris SE7,8, Deary IJ7,8, Marioni RE6,7, Soerensen M9,10,11, Mengel-From J9,10, Hjelmborg J9, Christensen K9,10, Wilson JG12,13, Levy D14,15, Reiner AP16, Chen W3, Li S17, Harris JR1,18, Magnus P18, Aviv A19, Jugessur A1,18,20, Horvath S5,21
Affiliation:
1Department of Genetics and Bioinformatics, Norwegian Institute of Public Health, Oslo, Norway.
2Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
3Department of Epidemiology, Tulane University, New Orleans, LA 70118, USA.
4Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.
5Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 9009, USA.
6Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
7Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
8Department of Psychology, University of Edinburgh, Edinburgh, UK.
9Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense C, Denmark.
10Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
11Center for Individualized Medicine in Arterial Diseases, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense C, Denmark.
12Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
13Department of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
14Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
15The Framingham Heart Study, Framingham, MA 01702, USA.
16Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
17Children's Minnesota Research Institute, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA.
18Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
19Center of Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA.
20Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
21Department of of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
Conference/Journal: Aging (Albany NY).
Date published: 2019 Aug 26
Other: Volume ID: 11 , Special Notes: doi: 10.18632/aging.102230. [Epub ahead of print] , Word Count: 208


Telomere length is associated with age-related diseases and is highly heritable. It is unclear, however, to what extent epigenetic modifications are associated with leukocyte telomere length (LTL). In this study, we conducted a large-scale epigenome-wide association study (EWAS) of LTL using seven large cohorts (n=5,713) - the Framingham Heart Study, the Jackson Heart Study, the Women's Health Initiative, the Bogalusa Heart Study, the Lothian Birth Cohorts of 1921 and 1936, and the Longitudinal Study of Aging Danish Twins. Our stratified analysis suggests that EWAS findings for women of African ancestry may be distinct from those of three other groups: males of African ancestry, and males and females of European ancestry. Using a meta-analysis framework, we identified DNA methylation (DNAm) levels at 823 CpG sites to be significantly associated (P<1E-7) with LTL after adjusting for age, sex, ethnicity, and imputed white blood cell counts. Functional enrichment analyses revealed that these CpG sites are near genes that play a role in circadian rhythm, blood coagulation, and wound healing. Weighted correlation network analysis identified four co-methylation modules associated with LTL, age, and blood cell counts. Overall, this study reveals highly significant relationships between two hallmarks of aging: telomere biology and epigenetic changes.

KEYWORDS: DNA methylation; leukocyte telomere length; multi-ancestry

PMID: 31461406 DOI: 10.18632/aging.102230

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