Accounting for Population Structure in Gene-by-Environment Interactions in Genome-Wide Association Studies Using Mixed Models.

Although genome-wide association studies (GWASs) have discovered numerous novel genetic variants associated with many complex traits and diseases, those genetic variants typically explain only a small fraction of phenotypic variance. Factors that account for phenotypic variance include environmental factors and gene-by-environment interactions (GEIs). Recently, several studies have conducted genome-wide gene-by-environment association analyses and demonstrated important roles of GEIs in complex traits. One of the main challenges in these association studies is to control effects of population structure that may cause spurious associations. Many studies have analyzed how population structure influences statistics of genetic variants and developed several statistical approaches to correct for population structure. However, the impact of population structure on GEI statistics in GWASs has not been extensively studied and nor have there been methods designed to correct for population structure on GEI statistics. In this paper, we show both analytically and empirically that population structure may cause spurious GEIs and use both simulation and two GWAS datasets to support our finding. We propose a statistical approach based on mixed models to account for population structure on GEI statistics. We find that our approach effectively controls population structure on statistics for GEIs as well as for genetic variants

Imputing Phenotypes for Genome-wide Association Studies

Genome-wide association studies (GWASs) have been successful in detecting variants correlated with phenotypes of clinical interest. However, the power to detect these variants depends on the number of individuals whose phenotypes are collected, and for phenotypes that are difficult to collect, the sample size might be insufficient to achieve the desired statistical power. The phenotype of interest is often difficult to collect, whereas surrogate phenotypes or related phenotypes are easier to collect and have already been collected in very large samples. This paper demonstrates how we take advantage of these additional related phenotypes to impute the phenotype of interest or target phenotype and then perform association analysis. Our approach leverages the correlation structure between phenotypes to perform the imputation. The correlation structure can be estimated from a smaller complete dataset for which both the target and related phenotypes have been collected. Under some assumptions, the statistical power can be computed analytically given the correlation structure of the phenotypes used in imputation. In addition, our method can impute the summary statistic of the target phenotype as a weighted linear combination of the summary statistics of related phenotypes. Thus, our method is applicable to datasets for which we have access only to summary statistics and not to the raw genotypes. We illustrate our approach by analyzing associated loci to triglycerides (TGs), body mass index (BMI), and systolic blood pressure (SBP) in the Northern Finland Birth Cohort dataset

Particle Physics Teaching Material: Charges, Interactions and Particles

This textbook is part of a four-volume series of teaching material on particle physics developed by the German Netzwerk Teilchenwelt in cooperation with the Joachim Herz Foundation. It covers the theoretical background of the Standard Model of particle physics in a didactically reduced way and primarily serves as a source of information for teachers, although the texts should be understandable for advanced or highly interested students as well. The three base concepts of the Standard Model, namely charges, interactions and particles as well as their dependencies are introduced. The focus of this educational approach is set to charges as the reasons for interactions. The spectrum of existing elementary particles plays a secondary role. In addition to educational advice concerning difficult terms and concepts, a spiral curriculum is outlined which allows to include aspects of particle physics on different degrees of difficulty throughout secondary and high school education. In this context, connections to common contents of physics curricula are pointed out. The volume also includes exercises for the use in class. The PDF file of the textbook can be downloaded here. Printed versions of the textbook can be ordered free of charge by contacting Netzwerk Teilchenwelt via [email protected]. All volumes of this teaching material can be downloaded at https://www.teilchenwelt.de/tp. A more comprehensive collection of teaching material can be found at https://www.teilchenwelt.de/material/materialien-fuer-lehrkraefte/

International Masterclasses - bringing LHC data to school children

International Masterclasses provide an opportunity for high school students to be “scientists for a day”. 15- to 19-year-old students in countries around the whole world are invited to one of about 160 nearby universities or research centres for one day in order to take part in an authentic research process. Lectures from active scientists give insight in topics and methods of basic research at the fundaments of matter and forces, enabling the students to perform measurements on real data from CERN's Large Hadron Collider. At the end of each day, like in an international research collaboration, the participants join in a video conference with other students groups and CERN for discussion and combination of their results. In 2013, about 10.000 students from 37 countries participated in the program. International Masterclasses are organised by IPPOG (International Particle Physics Outreach Group) and have the potential to add valuable experiences to physics education in school environments

Simultaneous Modeling of Disease Status and Clinical Phenotypes To Increase Power in Genome-Wide Association Studies

Genome-wide association studies have identified thousands of variants implicated in dozens of complex diseases. Most studies collect individuals with and without disease and search for variants with different frequencies between the groups. For many of these studies, additional disease traits are also collected. Jointly modeling clinical phenotype and disease status is a promising way to increase power to detect true associations between genetics and disease. In particular, this approach increases the potential for discovering genetic variants that are associated with both a clinical phenotype and a disease. Standard multivariate techniques fail to effectively solve this problem, because their case–control status is discrete and not continuous. Standard approaches to estimate model parameters are biased due to the ascertainment in case–control studies. We present a novel method that resolves both of these issues for simultaneous association testing of genetic variants that have both case status and a clinical covariate. We demonstrate the utility of our method using both simulated data and the Northern Finland Birth Cohort data

ATLAS W path - real data from the LHC for high school students

ATLAS W path is an educational scenario developed for high school students. They are introduced to basic concepts of particle identification and event classification. Students work with event displays from experimental data taken at the ATLAS detector. A dataset with 6000 real events has been made available. Measurement tasks include identifying particles to reveal the inner structure of the proton and to find the signature of the Higgs boson. ATLAS W path is widely used in International Masterclasses as well as in other educational scenarios

Accounting for Population Structure in Gene-by-Environment Interactions in Genome-Wide Association Studies Using Mixed Models.

Although genome-wide association studies (GWASs) have discovered numerous novel genetic variants associated with many complex traits and diseases, those genetic variants typically explain only a small fraction of phenotypic variance. Factors that account for phenotypic variance include environmental factors and gene-by-environment interactions (GEIs). Recently, several studies have conducted genome-wide gene-by-environment association analyses and demonstrated important roles of GEIs in complex traits. One of the main challenges in these association studies is to control effects of population structure that may cause spurious associations. Many studies have analyzed how population structure influences statistics of genetic variants and developed several statistical approaches to correct for population structure. However, the impact of population structure on GEI statistics in GWASs has not been extensively studied and nor have there been methods designed to correct for population structure on GEI statistics. In this paper, we show both analytically and empirically that population structure may cause spurious GEIs and use both simulation and two GWAS datasets to support our finding. We propose a statistical approach based on mixed models to account for population structure on GEI statistics. We find that our approach effectively controls population structure on statistics for GEIs as well as for genetic variants

Netzwerk Teilchenwelt - Jugendliche erfahren aktuelle physikalische Forschung

Es ist ein Ziel des Physikunterrichts und außerschulischer Lernorte, Jugendliche an aktuelle Themen der physikalischen Forschung heranzuführen. Ein wichtiger Aspekt hierbei ist die Forschungsmethode: Wie gewinnen Physiker heute Erkenntnisse, wie arbeiten sie? Ein seit etlichen Jahren durchgeführtes Programm, die Internationalen Hands on Particle Physics Masterclasses (im Folgenden Internationale Masterclasses)1 , zeigt gute Erfolge, dies zu vermitteln. Jugendliche analysieren nach einer Einführung in die Teilchenphysik reale Daten vom CERN und führen ihre Ergebnisse in einer internationalen Videokonferenz zusammen. Um dieses erfolgreiche, aber auch aufwändige Programm für einen breiteren Kreis an Jugendlichen zu öffnen, wurde es für den Einsatz in Schulklassen adaptiert. In dem seit 2010 vom BMBF geförderten "Netzwerk Teilchenwelt"2 werden aufbauende Angebote gemacht, um interessierte Jugendliche an die moderne Teilchenphysik heranzuführen

Resources for Education and Outreach Activities: discussion session

Over the past few years a variety of resources have been developed, by individuals and groups, to support Education & Outreach activities in particle physics. Following short (five-minute) presentations by six speakers, a discussion session allowed the audience to go further in depth in activities they found particularly interesting. This paper presents brief overviews from each of the six speakers, followed by a summary of the ensuing discussio