The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

Non-motor symptoms (NMSs) significantly contribute to increased morbidity and poor quality of life in patients with parkinsonian disorders. This study aims to explore the profile of NMSs in patients with progressive supranuclear palsy (PSP) using the validated Non-Motor Symptom Scale (NMSS). Seventy-six patients with PSP were evaluated in this study. Motor symptoms and NMSs were evaluated using the PSP Rating Scale (PSPRS), Unified Parkinson's Disease Rating Scale-III, Montreal Cognitive Assessment, Hamilton Depression (HAMD) and Anxiety Rating Scales, Parkinson's Disease Sleep Scale (PDSS) and NMSS. NMS severity and prevalence were also compared between patients with PSP-Richardson syndrome (PSP-RS) and those with PSP-parkinsonism. All subjects in this cohort reported at least 2 NMSs. The most prevalent NMSs in patients with PSP were in the domains of sleep/fatigue, mood/cognition, and sexual function. The least prevalent NMSs were in the domains of cardiovascular including falls, and perceptual problems/hallucinations. Significant correlations were observed between the NMSS scores and HAM-D, PDSS, PSPRS scores and PSPRS sub-scores. The severity of NMSs was unrelated to the duration of illness. Patients with PSP-RS reported a higher severity of drooling, altered smell/taste, depression and altered interest in sex and a higher prevalence of sexual dysfunction. NMSs are commonly observed in patients with PSP, and the domains of sleep, mood and sexual function are most commonly affected. These symptoms contribute significantly to disease morbidity, and clinicians should pay adequate attention to identifying and addressing these symptoms.

Objectives: The objective of this study was to assess the clinical characteristics, patterns, and factors associated with headache in patients with cerebral venous sinus thrombosis (CVT). Methods: In this prospective cohort study, we recruited conscious CVT patients who were able to give reliable history after consent. Institutional ethics approval was obtained. The diagnosis of CVT was based on the clinical and imaging parameters. Data regarding headache characteristic, severity (visual analog scale [VAS]), imaging findings and outcome was recorded. Results: Forty-seven patients (19 males and 28 females) with mean age 29.7 ± 8.7 years were recruited. The mean duration of headache was 12.6 ± 26.8 days, and VAS was 79.38 ± 13.41. Headache onset was acute in 51.1%, subacute in 42.6%, thunderclap in 4.3%, and chronic in 2.1%; location was holocranial in 36.2%, frontal in 27.7% patients; description was throbbing in 44.7% and aching in 25.5% patients. Superior sagittal sinus and transverse sinus were involved in 63.8% cases each. The prothrombotic factors were anemia in 55.3%, puerperal in 38.3%, hyperhomocysteinemia in 29.8%, and polycythemia in 19.1%. Conclusion: Holocranial and bifrontal headache of increasing severity may be a marker of CVT. This may be useful in clinical judgment in identifying conscious patients with CVT.