Abstract A85: Paternal age at birth is associated with leukocyte telomere length in the Nurses' Health Study

Abstract

Abstract Despite the high heritability of telomere length, genome-wide association studies have not found common genetic variants with a strong influence on telomere length. A few studies have demonstrated significant correlations between the telomere length of offspring and maternal and/or paternal telomere lengths. Positive correlations have also been observed for parental age at birth and offspring telomere length, particularly with paternal age. We decided to investigate the relationship between parental age and female offspring telomere length in one of the largest studies to date, by using existing leukocyte telomere length (LTL) data that were measured by a high-throughput quantitative PCR assay for multiple prospective nested case-control studies of various cancers and cardiovascular disease in the Nurses' Health Study (NHS). We derived probit scores for each nested case-control study to standardize for between-batch variability before pooling data. Participants included in this analysis were free of cancer and other major diseases at blood draw and were restricted to the 6,647 NHS participants who reported the years their mother and father were born on the 1976 baseline questionnaire. We calculated Spearman correlation coefficients and also used generalized linear regression to calculate least-square (LS) means of LTL probit score by maternal and paternal age at birth categories. LS means were adjusted for the participant's age at blood draw. Analyses of maternal age at birth categories were additionally adjusted for continuous paternal age at birth and vice versa. The mean age of participants at blood draw was 59 years. Mean maternal and paternal age at birth were 28 and 32 years, respectively. Maternal age and paternal age at birth were highly correlated (rS=0.77, P<0.0001). After controlling for participant's age at blood draw and maternal age at birth, paternal age at birth was positively associated with the participant's LTL at blood draw (P-trend=0.003). The adjusted LS mean LTL (probit score) across paternal age categories (15–24, 25–29, 30–34, 35–39, 40–44, and 45+ years) were −0.10, −0.01, 0.01, 0.02, 0.08, and 0.19, respectively. Among the NHS participants, a one year increase in paternal age at birth corresponded to an LT L difference observed for ∼6 months of younger age. Maternal age at birth was not associated with the participant's LTL at blood draw (P-trend=0.26). In our study population, we provide evidence of an association between older paternal age at birth and longer telomere length among female offspring, but not for maternal age at birth. These results are consistent with prior literature and support the existence of temporally-regulated paternal factors in the inheritance of leukocyte telomere length among their female offspring. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A85.