A Cautionary Note on the Effects of Population Stratification Under an Extreme Phenotype Sampling Design

Extreme phenotype sampling (EPS) is a popular study design used to reduce genotyping or sequencing costs. Assuming continuous phenotype data are available on a large cohort, EPS involves genotyping or sequencing only those individuals with extreme phenotypic values. Although this design has been shown to have high power to detect genetic effects even at smaller sample sizes, little attention has been paid to the effects of confounding variables, and in particular population stratification. Using extensive simulations, we demonstrate that the false positive rate under the EPS design is greatly inflated relative to a random sample of equal size or a “case-control”-like design where the cases are from one phenotypic extreme and the controls randomly sampled. The inflated false positive rate is observed even with allele frequency and phenotype mean differences taken from European population data. We show that the effects of confounding are not reduced by increasing the sample size. We also show that including the top principal components in a logistic regression model is sufficient for controlling the type 1 error rate using data simulated with a population genetics model and using 1,000 Genomes genotype data. Our results suggest that when an EPS study is conducted, it is crucial to adjust for all confounding variables. For genetic association studies this requires genotyping a sufficient number of markers to allow for ancestry estimation. Unfortunately, this could increase the costs of a study if sequencing or genotyping was only planned for candidate genes or pathways; the available genetic data would not be suitable for ancestry correction as many of the variants could have a true association with the trait

Extending Rare Variant Association Tests in Affected Siblings to Account for Background Genetic Risk

Complex diseases are thought to be caused by both common and rare variants. Family studies are typically used to detect inherited rare variants associated with disease while population-based studies are used to identify common variants. Population-based studies have led to the development of individual-level genetic risk scores (GRS), aggregates of putative common susceptibility variants derived from genome-wide association studies. Currently, rare variant tests of affected sibling pairs (ASPs) do not include the background disease risk from common variants. We demonstrate how to extend existing rare variant ASP tests to include GRS of common variants and report simulations that evaluate: (1) validity of the methods and (2) relative efficacy of considering risk from common variants when testing for rare variant association in family settings. We apply the methods to whole-exome sequence data of sisters ascertained on early-onset breast cancer and incorporate a recently reported breast cancer GRS.M.Sc

A proposito di spazio, limite, reinvenzione

Qusto libro include 60 profili di artiste nell'area romana e non solo; contributi critici di 15 fra studiose e studiosi di discipline storico-artistiche, filosofiche, sociologiche, antropologiche, psicologiche. Questi sono i numeri di FEMM[E]: un progetto - e un libro - nato sotto la denominazione e l'intento di una "ricerca sulla specificità (eventuale) dell'arte femminile", realizzata dal 2016 al 2018 su iniziativa e cura della storica dell'arte Anna Maria Panzera e dell'artista Veronica Montanino. Il mio testo parla del tema dell'abitazione e in specifico di «casa» che è riccorente nelle opere di artiste in tutto il mondo. Dopo gli esempi conosciuti della storia dell'arte contemporanea, il testo prosegue con le storie degli artisti con cui l'autrice ha collaborato sul tema di "Casa"