Polygenic risk score of shorter telomere length and risk of depression and anxiety in women

Abstract

Prior studies have reported significant cross-sectional associations between depression or anxiety and shorter telomere lengths, but the temporality of associations is uncertain. Little is known regarding whether shorter telomere length is related to increased risk of developing depression or anxiety. In this study, using the genetic tool of polygenic risk score (PRS), we evaluated the association between genetic predisposition to shorter telomere length and the risks of lifetime clinically significant depression (defined by self-reported clinician/physician diagnosis, antidepressant use, and/or presence of severe depressive symptoms) and of clinically meaningful anxiety symptoms among 17,693 female participants of European ancestry. The weighted PRS of telomere lengths (TLs) combined the dosage of nine alleles that were significantly associated with inter-individual variation in TLs in published genome-wide association studies. Higher score of PRS, corresponding to shorter TL in the literature, was significantly associated with shorter relative TLs (p = 0.008). However, higher PRS was not associated with the lifetime risk of either depression or anxiety. Furthermore, higher PRS was not associated with long-term patterns of depressive symptom trajectories or specifically with later-life onset of depression or anxiety. In summary, this study did not observe a significant association between genetic predisposition to shorter telomere length and risk of depression and anxiety in a large sample of mid-life and older white women. However, these genetic variants jointly account for a limited proportion of interpersonal variation in leukocyte telomere length. Future studies will need to incorporate more genetic variants to improve the accuracy of predicted power, as such data become available.

Genetically predicted telomere length is associated with clonal somatic copy number alterations in peripheral leukocytes

“…This genetic approach to estimate telomere length does not contain the biases generally attributable to measured telomere length (e.g., differences in DNA extraction or storage [24]). Several studies have demonstrated the power of this approach to identify associations between telomere length and a variety of outcomes [2,[10][11][12][13]25,26]. Additionally, previous studies that have derived gTL using a PRS have incorporated variant weights from several different genome-wide association studies (GWAS) [2,10,11], which may lead to uncomparable weight estimates due to study specific differences.…”

Stress‐Busting Program for Family Caregivers: Validation of the Spanish version using biomarkers and quality‐of‐life measures

“…Shorter leukocyte telomere length has been associated with psychological stress, depression, posttraumatic syndrome, and many other systemic conditions. It is unknown whether telomere length is shortened in caregivers as compared to heathy controls (Chang et al, 2018;Oliveira et al, 2016). The possibility of reversing the deleterious effects of telomere shortening in leukocytes has been suggested in several studies with the reversal possible through diet interventions (Carulli et al, 2016;Verhoeven et al, 2014).…”

Mood Disorders, Accelerated Aging, and Inflammation: Is the Link Hidden in Telomeres?

“…These results suggest that the genetic risk for shortened LTL is able to increase the risk for MDD, and specifically for childhood-onset MDD [67]. Conversely, a recent study did not find any association between a polygenic risk score, including nine SNPs that were previously associated with inter-individual variation in TL [17,18,68] and the risk of lifetime depression in a large sample of 17,693 female participants of European ancestry from the Nurses' Health Study (NHS) [69]. Potential explanations of the discrepancies observed among the studies might be found in the different definitions used to define MDD, as well as in our still-limited knowledge of genetic variants that are able to explain inter-individual variability in TL.…”