Telomere length as a modifier of age-at-onset in Huntington disease: a two-sample Mendelian randomization study
Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the HTT gene. Despite a strong inverse association between mutant HTT CAG repeat size and age-at-onset, there is a large residual variability in disease onset which is attributable to other modifying genetic or environmental factors . Telomeres are repetitive sequences of nucleotides at the end of chromosomes protecting them from degeneration or fusion with neighboring chromosomes. Recently, shortened telomeres were reported in HD patients compared to matched controls . Because shortened telomeres have been associated with an increased risk of several neuropsychiatric and neurodegenerative disorders , we hypothesized that telomere length could also be a modifier of age-at-onset in HD.
We performed a two-sample Mendelian randomization (MR) study; a recently developed statistical method which allows assessment of the effects of an...
Compliance with ethical standards
Conflicts of interest
Dr Aziz and Dr Weydt report no conflicts of interest.