The molecular basis of lactase persistence: Linking genetics and epigenetics.

Lactase persistence (LP) - the genetic trait that determines the continued expression of the enzyme lactase into adulthood - has undergone recent, rapid positive selection since the advent of animal domestication and dairying in some human populations. While underlying evolutionary explanations have been widely posited and studied, the molecular basis of LP remains less so. This review considers the genetic and epigenetic bases of LP.

Accuracy of routinely collected hospital administrative discharge data and death certificate ICD-10 diagnostic coding in progressive supranuclear palsy and corticobasal syndrome: a systematic review and validation study.

Background: We conducted a systematic review to identify existing ICD-10 coding validation studies in progressive supranuclear palsy and corticobasal syndrome [PSP/CBS]) and, in a new study, evaluated the accuracy of ICD-10 diagnostic codes for PSP/CBS in Scottish hospital inpatient and death certificate data.

Methods: Original studies that assessed the accuracy of specific ICD-10 diagnostic codes in PSP/CBS were sought. Separately, we estimated the positive predictive value (PPV) of specific codes for PSP/CBS in inpatient hospital data (SMR01, SMR04) compared to clinical diagnosis in four regions.

Total Patient Delay: A Comparison of Patient and Clinician/Health System Delays in the Diagnosis of Progressive Supranuclear Palsy and Corticobasal Syndrome.

Background: Early diagnosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) is important for clinical care and key to developing successful disease-modifying agents. The patient-dependent phases of decision-making made before contact with a healthcare professional have been inadequately studied.

Objectives: To evaluate the patient-dependent phases of decision-making from symptom onset, comparing this to clinician and/or health system delays within the overall diagnostic pathway.

The hazards of genotype imputation when mapping disease susceptibility variants.

Background: The cost-free increase in statistical power of using imputation to infer missing genotypes is undoubtedly appealing, but is it hazard-free? This case study of three type-2 diabetes (T2D) loci demonstrates that it is not; it sheds light on why this is so and raises concerns as to the shortcomings of imputation at disease loci, where haplotypes differ between cases and reference panel.

Results: T2D-associated variants were previously identified using targeted sequencing. We removed these significantly associated SNPs and used neighbouring SNPs to infer them by imputation.

The evolution of diagnosis from symptom onset to death in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) compared to Parkinson's disease (PD).

Background: Misdiagnosis and delayed diagnosis in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are common. Few studies have systematically evaluated the diagnostic process from symptom onset to death in representative cohorts.

Methods: All PSP/CBD cases (n = 28/2) and age-sex matched Parkinson's disease (PD) cases (n = 30) were identified from a UK prospective incident Parkinsonism cohort.