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: <sup>1</sup>Department of Genetics and Bioinformatics, Norwegian Institute of Public Health, Oslo, Norway.
<sup>2</sup>Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
<sup>3</sup>Department of Epidemiology, Tulane University, New Orleans, LA 70118, USA.
<sup>4</sup>Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.
<sup>5</sup>Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 9009, USA.
<sup>6</sup>Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
<sup>7</sup>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
<sup>8</sup>Department of Psychology, University of Edinburgh, Edinburgh, UK.
<sup>9</sup>Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense C, Denmark.
<sup>10</sup>Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
<sup>11</sup>Center for Individualized Medicine in Arterial Diseases, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense C, Denmark.
<sup>12</sup>Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
<sup>13</sup>Department of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
<sup>14</sup>Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
<sup>15</sup>The Framingham Heart Study, Framingham, MA 01702, USA.
<sup>16</sup>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
<sup>17</sup>Children's Minnesota Research Institute, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA.
<sup>18</sup>Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
<sup>19</sup>Center of Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA.
<sup>20</sup>Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
<sup>21</sup>Department 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