The heritability of leucocyte telomere length dynamics

Background Leucocyte telomere length (LTL) is a complex trait associated with ageing and longevity. LTL dynamics are defined by LTL and its age-dependent attrition. Strong, but indirect evidence suggests that LTL at birth and its attrition during childhood largely explains interindividual LTL variation among adults. A number of studies have estimated the heritability of LTL, but none has assessed the heritability of age-dependent LTL attrition. Methods We examined the heritability of LTL dynamics based on a longitudinal evaluation (an average follow-up of 12 years) in 355 monozygotic and 297 dizygotic same-sex twins (aged 19–64 years at baseline). Results Heritability of LTL at baseline was estimated at 64% (95% CI 39% to 83%) with 22% (95% CI 6% to 49%) of shared environmental effects. Heritability of age-dependent LTL attrition rate was estimated at 28% (95% CI 16% to 44%). Individually unique environmental factors, estimated at 72% (95% CI 56% to 84%) affected LTL attrition rate with no indication of shared environmental effects. Conclusions This is the first study that estimated heritability of LTL and also its age-dependent attrition. As LTL attrition is much slower in adults than in children and given that having a long or a short LTL is largely determined before adulthood, our findings suggest that heritability and early life environment are the main determinants of LTL throughout the human life course. Thus, insights into factors that influence LTL at birth and its dynamics during childhood are crucial for understanding the role of telomere genetics in human ageing and longevity.

[1]  C. Dalgård,et al.  Sex difference in leukocyte telomere length is ablated in opposite-sex co-twins , 2014, International journal of epidemiology.

[2]  A. Hofman,et al.  Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers , 2014, International journal of epidemiology.

[3]  T. Spector,et al.  Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect , 2013, European Journal of Human Genetics.

[4]  E. Susser,et al.  Tracking and fixed ranking of leukocyte telomere length across the adult life course , 2013, Aging cell.

[5]  P. O’Reilly,et al.  Identification of seven loci affecting mean telomere length and their association with disease , 2013, Nature Genetics.

[6]  E. Susser,et al.  Telomeres shorten at equivalent rates in somatic tissues of adults , 2013, Nature Communications.

[7]  A. Aviv,et al.  Leukocyte telomere dynamics in the elderly , 2013, European Journal of Epidemiology.

[8]  L. Christiansen,et al.  Twins for epigenetic studies of human aging and development , 2013, Ageing Research Reviews.

[9]  M. Nalls,et al.  Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans , 2012, Human molecular genetics.

[10]  P. Lansdorp,et al.  Collapse of Telomere Homeostasis in Hematopoietic Cells Caused by Heterozygous Mutations in Telomerase Genes , 2012, PLoS genetics.

[11]  A. Aviv Genetics of leukocyte telomere length and its role in atherosclerosis. , 2012, Mutation research.

[12]  E. Epel,et al.  Telomeres and lifestyle factors: roles in cellular aging. , 2012, Mutation research.

[13]  A. Aviv,et al.  Energy intake and leukocyte telomere length in young adults. , 2012, The American journal of clinical nutrition.

[14]  A. Aviv,et al.  Synchrony of telomere length among hematopoietic cells. , 2010, Experimental hematology.

[15]  C. Harley,et al.  Measurement of telomere length by the Southern blot analysis of terminal restriction fragment lengths , 2010, Nature Protocols.

[16]  Andrew D. Johnson,et al.  Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology , 2010, Proceedings of the National Academy of Sciences.

[17]  T. Spector,et al.  Common variants near TERC are associated with mean telomere length , 2010, Nature Genetics.

[18]  Thomas Widmann,et al.  Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall , 2009, Circulation.

[19]  Igor Sidorov,et al.  Leukocyte telomere dynamics and human hematopoietic stem cell kinetics during somatic growth. , 2009, Experimental hematology.

[20]  A. Aviv,et al.  Leukocyte telomeres are longer in African Americans than in whites: the National Heart, Lung, and Blood Institute Family Heart Study and the Bogalusa Heart Study , 2008, Aging cell.

[21]  J. Vaupel,et al.  Telomere length and mortality: a study of leukocytes in elderly Danish twins. , 2008, American journal of epidemiology.

[22]  D. Levy,et al.  Association of Leukocyte Telomere Length With Circulating Biomarkers of the Renin-Angiotensin-Aldosterone System: The Framingham Heart Study , 2008, Circulation.

[23]  T. Spector,et al.  The association between physical activity in leisure time and leukocyte telomere length. , 2008, Archives of internal medicine.

[24]  T. Spector,et al.  Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm , 2008, PLoS genetics.

[25]  K. Mossman The Wellcome Trust Case Control Consortium, U.K. , 2008 .

[26]  G. De Backer,et al.  Paternal age at birth is an important determinant of offspring telomere length. , 2007, Human molecular genetics.

[27]  G. Mcclearn,et al.  Telomere length predicts survival independent of genetic influences , 2007, Aging cell.

[28]  P. Visscher,et al.  Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome? , 2007, Diabetologia.

[29]  T. Spector,et al.  The effects of social status on biological aging as measured by white‐blood‐cell telomere length , 2006, Aging cell.

[30]  T. Spector,et al.  Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs. , 2006, American journal of human genetics.

[31]  A. Akkad,et al.  Telomere length in small‐for‐gestational‐age babies , 2006, BJOG : an international journal of obstetrics and gynaecology.

[32]  A. Aviv,et al.  Obesity, cigarette smoking, and telomere length in women , 2005, The Lancet.

[33]  A. Aviv,et al.  Rise in Insulin Resistance Is Associated With Escalated Telomere Attrition , 2005, Circulation.

[34]  K. Riabowol,et al.  Paternal age is positively linked to telomere length of children , 2005, Aging cell.

[35]  Andrea H. Mason,et al.  Mapping of a major locus that determines telomere length in humans. , 2005, American journal of human genetics.

[36]  Peter Guttorp,et al.  Estimating human hematopoietic stem cell kinetics using granulocyte telomere lengths. , 2004, Experimental hematology.

[37]  J. Staessen,et al.  Telomere length and possible link to X chromosome , 2004, The Lancet.

[38]  P. Visscher,et al.  Twin study of genetic and environmental influences on glucose tolerance and indices of insulin sensitivity and secretion , 2003, Diabetologia.

[39]  R. Cawthon,et al.  Association between telomere length in blood and mortality in people aged 60 years or older , 2003, The Lancet.

[40]  J. Skurnick,et al.  Telomere Length in the Newborn , 2002, Pediatric Research.

[41]  J. Skurnick,et al.  Telomere length inversely correlates with pulse pressure and is highly familial. , 2000, Hypertension.

[42]  P. Lansdorp,et al.  Telomerase activity in candidate stem cells from fetal liver and adult bone marrow. , 1998, Blood.

[43]  P. Sham Statistics in human genetics , 1997 .

[44]  I. Weissman,et al.  Telomerase activity in hematopoietic cells is associated with self-renewal potential. , 1996, Immunity.

[45]  C. Harley,et al.  Differential Expression of Telomerase Activity in Hematopoietic Progenitors from Adult Human Bone Marrow , 1996, Stem cells.

[46]  D I Boomsma,et al.  Genetic determination of telomere size in humans: a twin study of three age groups. , 1994, American journal of human genetics.

[47]  A. Thapar,et al.  Methodology for Genetic Studies of Twins and Families , 1993 .

[48]  G. Vogler,et al.  Methodology for genetic studies of twins and families , 1993 .

[49]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.