Huntington’s disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by CAG repeats expansion. There is a paucity of comprehensive clinical analysis in Chinese HD patients due to the low prevalence of HD in Asia. We aimed to comprehensively describe the motor, neuropsychiatric symptoms, and functional assessment in patients with HD from China. A total of 205 HD patients were assessed by the Unified Huntington’s Disease Rating Scale (UHDRS), the short version of Problem-Behavior Assessment (PBA-s), Hamilton Depression Scale (HAMD) and Beck Depression Inventory (BDI). Multivariate logistic regression analysis was used to explore the independent variables correlated with neuropsychiatric subscales. The mean age of motor symptom onset was 41.8 ± 10.0 years old with a diagnostic delay of 4.3 ± 3.8 years and a median CAG repeats of 44. The patients with a positive family history had a younger onset and larger CAG expansion than the patients without a family history (p < 0.05). There was a significant increase in total motor score across disease stages (p < 0.0001). Depression (51%) was the most common neuropsychiatric symptom at all stages, whereas moderate to severe apathy commonly occurred in advanced HD stages. We found lower functional capacity and higher HAMD were independently correlated with irritability; higher HAMD and higher BDI were independently correlated with affect; male sex and higher HAMD were independently correlated with apathy. In summary, comprehensive clinical profile analysis of Chinese HD patients showed not only chorea-like movement, but psychiatric symptoms were outstanding problems and need to be detected early. Our study provides the basis to guide clinical practice, especially in practical diagnostic and management processes.

Multiple evidence from epidemiological studies has suggested association between physical activity and risk of multiple sclerosis (MS). However, the conclusion was still controversial between studies, and whether the association was causal or confounded is elusive. To evaluate the role of physical activity with different intensities in the risk of MS, we first estimated their genetic correlation, and then conducted two-sample and multivariable Mendelian randomization analyses based on summary statistics from previous large genome-wide association studies. A significant genetic correlation was identified between moderate physical activity and the risk of MS (genetic correlation: -0.15, SE=0.05, P=2.9E-03). Meanwhile, higher moderate physical activity was significantly associated with a reduced risk of MS (OR:0.87, 95% CI:0.80-0.96, P=3.45E-03). Such association was further verified using summary statistics from another study on overall physical activity (OR:0.36, 95% CI:0.17-0.76, P=6.82E-03). The results were robust under all sensitivity analyses. Current results suggested moderate physical activity could reduce the risk of MS. These findings help better understand the role of physical activity in MS, and provide some lifestyle recommendations for individuals susceptible to MS.

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Background Recently, several rare variants of SPTLC1 were identified as disease cause for juvenile amyotrophic lateral sclerosis (ALS) by disrupting the normal homeostatic regulation of serine palmitoyltransferase (SPT). However, further exploration of the rare variants in large cohorts was still necessary. Meanwhile, SPTLC2 plays a similar role as SPTLC1 in the SPT function. Methods To explore the genetic role of SPTLC1 and SPTLC2 in ALS, we analyzed the rare protein-coding variants in 2011 patients with ALS and 3298 controls from the Chinese population with whole exome sequencing. Fisher’s exact test was performed between each variant and disease risk, while at gene level over-representation of rare variants in patients was examined with optimized sequence kernel association test (SKAT-O). Results Totally 33 rare variants with minor allele frequency < 0.01 were identified, including 17 in SPTLC1 and 16 in SPTLC2. One adult-onset patient carried the variant p.E406K (SPTLC1) which was reported in previous study. Additionally, three adult-onset patients carried variants in the same amino acids as the variants identified in previous studies (p.Y509C, p.S331T, and p.R239Q in SPTLC1). At gene level, rare variants of SPTLC1 and STPLC2 were not enriched in patients. Conclusion These results broadened the variant spectrum of SPTLC1 and SPTLC2 in ALS, and paved the way for future research. Further replication was still needed to explore the genetic role of SPTLC1 in ALS.