Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

• Published in: European journal of human genetics : EJHG Vol. 21; no. 10; pp. 1163 - 1168
• Main Authors: Broer, Linda, Codd, Veryan, Nyholt, Dale R, Deelen, Joris, Mangino, Massimo, Willemsen, Gonneke, Albrecht, Eva, Amin, Najaf, Beekman, Marian, de Geus, Eco J C, Henders, Anjali, Nelson, Christopher P, Steves, Claire J, Wright, Margie J, de Craen, Anton J M, Isaacs, Aaron, Matthews, Mary, Moayyeri, Alireza, Montgomery, Grant W, Oostra, Ben A, Vink, Jacqueline M, Spector, Tim D, Slagboom, P Eline, Martin, Nicholas G, Samani, Nilesh J, van Duijn, Cornelia M, Boomsma, Dorret I
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.10.2013
• Subjects: Adolescent; Adult; Age; Age Factors; Aged; Aged, 80 and over; Aging; Birth; Case-Control Studies; Cell division; Deoxyribonucleic acid; DNA; Epidemiology; Estimates; Families & family life; Female; Genetic factors; Genetics; Heredity; Heritability; Humans; Hypertension; Inheritance Patterns; Male; Maternal inheritance; Medical research; Meta-analysis; Middle Aged; Mortality; Paternal Age; Pedigree; Population; Progeny; Studies; Telomerase; Telomere - genetics; Telomere Shortening - genetics; Twins; Twins - genetics; Netherlands; United Kingdom > UK; Queensland Australia; United States > US
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/ejhg.2012.303

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19,713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64-0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother-offspring (r=0.42; P-value=3.60 × 10(-61)) than father-offspring correlation (r=0.33; P-value=7.01 × 10(-5)), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10(-5)). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10(-30)) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10(-23)) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10(-10)). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.