Common Variation in Cytoskeletal Genes Is Associated with Conotruncal Heart Defects

There is strong evidence for a genetic contribution to non-syndromic congenital heart defects (CHDs). However, exome- and genome-wide studies conducted at the variant and gene-level have identified few genome-wide significant CHD-related genes. Gene-set analyses are a useful complement to such studies and candidate gene-set analyses of rare variants have provided insight into the genetics of CHDs. However, similar analyses have not been conducted using data on common genetic variants. Consequently, we conducted common variant analyses of 15 CHD candidate gene-sets, using data from two common types of CHDs: conotruncal heart defects (1431 cases) and left ventricular outflow tract defects (509 cases). After Bonferroni correction for evaluation of multiple gene-sets, the cytoskeletal gene-set was significantly associated with conotruncal heart defects (βS = 0.09; 95% confidence interval (CI) 0.03–0.15). This association was stronger when analyses were restricted to the sub-set of cytoskeletal genes that have been observed to harbor rare damaging genotypes in at least two CHD cases (βS = 0.32, 95% CI 0.08–0.56). These findings add to the evidence linking cytoskeletal genes to CHDs and suggest that, for cytoskeletal genes, common variation may contribute to the risk of CHDs.

Complete Unilateral Absence of Trapezius Muscle

Congenital partial absence of the trapezius muscle is a relatively common variation. Several cases of partial absence of the trapezius muscle have been reported. However, complete unilateral agenesis of this muscle has not been previously reported. In our case, a complete cadaver dissection of an 87-year-caucasian male was performed at the Department of Anatomy, College of Medicine in Saskatoon, Canada. The entire body dissection revealed a complete agenesis of the left trapezius muscle fibers. No other significant congenital anomalies were found.

Common variation at the LRRK2 locus is associated with survival in the primary tauopathy progressive supranuclear palsy

The genetic basis of variation in the rate of disease progression of primary tauopathies has not been determined. In two independent progressive supranuclear palsy cohorts, we show that common variation at the LRRK2 locus determines survival from motor symptom onset to death, possibly through regulation of gene expression. This links together genetic risk in alpha-synuclein and tau disorders, and suggests that modulation of proteostasis and neuro-inflammation by LRRK2 inhibitors may have a therapeutic role across disorders.