Low Birth Weight in MZ Twins Discordant for Birth Weight is Associated with Shorter Telomere Length and lower IQ, but not Anxiety/Depression in Later Life

Abstract

Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intrapair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.

Recognition of a sequence: more growth before birth, longer telomeres at birth, more lean mass after birth

“…The present results align well with recent findings in twins discordant for birthweight : in monozygotic newborns with intra‐pair birthweight differences as little as between 0.1 and 0.3 kg, the heavier twin had longer telomeres, and the intra‐pair differences in birthweight correlated with the intra‐pair differences in telomere length; however, in dizygotic pairs with similarly discordant birthweights, no difference in telomere length was readily detectable, suggesting that genetic variation contributes more than minor environmental influences to the neonatal variation of telomere length. The present study design – with birthweight differences averaging as much as 1.0 kg or 2.4 Z‐scores between SGA, AGA and LGA subgroups – allowed to disclose that heavier singletons also have longer telomeres at birth than lighter singletons.…”

“…The present results align well with recent findings in twins discordant for birthweight (17): in monozygotic newborns with intra-pair birthweight differences as little as between 0.1 and 0.3 kg, the heavier twin had Figure 2 Correlations between telomere length at birth (expressed as normalized T/S ratio) and, respectively, lean mass (left panels) and fat mass (right panels) at ages 2 weeks (upper panels) and 12 months (lower panels), in the same 60 nonobese infants born large, appropriate or small for gestational age (LGA, AGA or SGA). P-values are from Pearson correlations, adjusted for sex and age.…”

The known genetic loci for telomere length may be involved in the modification of telomeres length after birth

“…Researchers also have indicated that there were no difference between the RTL of preterm neonates and full-term newborns35. In addition, several studies observed that higher birth weight was associated with longer RTL3637, but which were inconsistent with our findings. Possible reason is that intra-uterine variables that affect newborn RTL are extremely complex, maternal psychosocial stress38, maternal estriol concentrations39, maternal Folate Concentrations40 and undetected factors might play an important role in affecting newborn RTL and disturbed the correlation between birth weight and RTL.…”

Association of birth outcomes and postnatal growth with adult leukocyte telomere length: Data from New Delhi Birth Cohort

“…As against the abovementioned studies, Strohmaier et al (2015) reported association of telomere length with birthweight in 16-yearold monozygotic twins but not seen in dizygotic twins. Raqib et al throughout life.…”

“…As against the abovementioned studies, Strohmaier et al () reported association of telomere length with birthweight in 16‐year‐old monozygotic twins but not seen in dizygotic twins. Raqib et al () reported significantly shorter lymphocyte TL in 5 years old preschool children ( n = 132) born with low birthweight compared with normal birthweight and suggested that this may be due to persistent immune activation because of high infection rate leading to higher T cell turnover.…”