LD Score regression distinguishes confounding from polygenicity in genome-wide association studies

Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from a true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size.

Compositional Data Analysis in Forensic Geoscience

Statistics are regularly used to make some form of comparison between trace evidence or deploy the exclusionary principle (Morgan and Bull, 2007) in forensic investigations. Trace evidence are routinely the results of particle size, chemical or modal analyses and as such constitute compositional data. The issue is that compositional data including percentages, parts per million etc. only carry relative information. This may be problematic where a comparison of percentages and other constraint/closed data is deemed a statistically valid and appropriate way to present trace evidence in a court of law. Notwithstanding an awareness of the existence of the constant sum problem since the seminal works of Pearson (1896) and Chayes (1960) and the introduction of the application of log-ratio techniques (Aitchison, 1986; Pawlowsky-Glahn and Egozcue, 2001; Pawlowsky-Glahn and Buccianti, 2011; Tolosana-Delgado and van den Boogaart, 2013) the problem that a constant sum destroys the potential independence of variances and covariances required for correlation regression analysis and empirical multivariate methods (principal component analysis, cluster analysis, discriminant analysis, canonical correlation) is all too often not acknowledged in the statistical treatment of trace evidence. Yet the need for a robust treatment of forensic trace evidence analyses is obvious. This research examines the issues and potential pitfalls for forensic investigators if the constant sum constraint is ignored in the analysis and presentation of forensic trace evidence. Forensic case studies involving particle size and mineral analyses as trace evidence are used to demonstrate the use of a compositional data approach using a centred log-ratio (clr) transformation and multivariate statistical analyses.

Intraocular pressure, central corneal thickness, and glaucoma in chinese adults: the liwan eye study.

PURPOSE: To describe the distribution of central corneal thickness (CCT), intraocular pressure (IOP), and their determinants and association with glaucoma in Chinese adults.DESIGN: Population-based cross-sectional study.METHODS: Chinese adults aged 50 years and older were identified using cluster random sampling in Liwan District, Guangzhou. CCT (both optical [OCCT] and ultrasound [UCCT]), intraocular pressure (by Tonopen, IOP), refractive error (by autorefractor, RE), radius of corneal curvature (RCC), axial length (AL), and body mass index (BMI) were measured, and history of hypertension and diabetes (DM) was collected by questionnaire. Right eye data were analyzed.RESULTS: The mean values of OCCT, UCCT, and IOP were 512 ± 29.0 μm, 542 ± 31.4 μm, and 15.2 ± 3.1 mm Hg, respectively. In multiple regression models, CCT declined with age (P < .001) and increased with greater RCC (P < .001) and DM (P = .037). IOP was positively associated with greater CCT (P < .001), BMI (P < .001), and hypertension (P < .001). All 25 persons with open-angle glaucoma had IOP <21 mm Hg. CCT did not differ significantly between persons with and without open- or closed-angle glaucoma. Among 65 persons with ocular hypertension (IOP >97.5th percentile), CCT (555 ± 29 μm) was significantly (P = .01) higher than for normal persons.CONCLUSIONS: The distributions of CCT and IOP in this study are similar to that for other Chinese populations, though IOP was lower than for European populations, possibly due to lower BMI and blood pressure. Glaucoma with IOP <21 mm Hg is common in this population. We found no association between glaucoma and CCT, though power (0.3) for this analysis was low.