A Practical Introduction to Statistical Genetics

Sponsored by the MGH Division of Clinical Research

Brief description: This course provides a comprehensive introduction to modern statistical genetics and covers widely-used genetic analysis methods including genome-wide association studies (GWAS), statistical fine-mapping, polygenic risk score analysis, heritability and genetic correlation analyses, Mendelian randomization, transcriptome-wide association studies (TWAS), sequencing data analysis and genomic research using publicly available biobank resources. The course focuses on statistical analysis of large-scale genetic datasets, with an outlook to cutting-edge research and state-of-the-art statistical genetics methods. The course is a modified version of a genomic epidemiology workshop initiated and designed by Chia-Yen Chen, Hailiang Huang and colleagues, which has been offered in multiple cities in China over the past few years.

Format: 10 90-min sessions; one session per week. The lectures will cover both theory and applications essential to statistical genetics.

Target audience: Investigators, fellows, students and clinicians who wish to expand their toolsets and conduct statistical analysis of large-scale genetic datasets to explore the genetic basis of complex traits and diseases. Basic knowledge of modern concepts in genetics, genomics and statistics is required. Beginning investigators who do not have experience with genetic approaches to complex traits are recommended to first take the course “A Primer on Complex Trait Genetics” offered and sponsored by the MGH Division of Clinical Research.

Upcoming


MGH Division of Clinical Research

A Practical Introduction to Statistical Genetics: Introduction to Sequencing Data Analysis

Topics: next generation sequencing and exome sequencing; common vs. rare variants; alignment and variant calling, filtering and quality control; variant annotation (protein-truncating, damaging missense, benign missense, synonymous); single variant association; gene-based collapsing methods; gene-set burden tests Speaker: Anne Feng

MGH Division of Clinical Research

A Practical Introduction to Statistical Genetics: Conducting Genomic Research Using Biobanks

Topics: UK Biobank, eMERGE network and Partners HealthCare Biobank, All of Us Research Program, genetic research using electronic health records (EHR) Speaker: Jordan Smoller

No Current Offerings


MGH Division of Clinical Research

A Practical Introduction to Statistical Genetics- Introduction

Session 1: Introduction Topics: overview of the course Speaker: Tian Ge A Practical Introduction to Statistical Genetics Sponsored by the MGH Division of Clinical Research Brief description: This course provides a comprehensive introduction to modern statistical genetics and covers widely-used …

MGH Division of Clinical Research

A Practical Introduction to Statistical Genetics: Heritability and Genetic Correlation Analyses

Topics: definition of broad-sense/narrow-sense heritability; twin and pedigree studies; SNP heritability; linear mixed effects modeling and GCTA; heritability estimation using GWAS summary statistics – LD score regression; liability model and case-control data analysis; variance partitioning; pleiotropy and genetic correlation; bivariate …

MGH Division of Clinical Research

A Practical Introduction to Statistical Genetics: Polygenic Risk Scores (PRS)

Topics: polygenic model of complex traits and disease susceptibility; discovery (training), validation and target (testing) samples; calculation of PRS – p-value informed clumping and thresholding; evaluation (performance metrics – variance explained, odds ratio, AUC, precision-recall curve) and interpretation; software and …

MGH Division of Clinical Research

A Practical Introduction to Statistical Genetics: Transcriptome and TWAS

Topics: non-coding GWAS SNPs; gene expression regulation; tissue-specific expression quantitative trait loci (eQTLs); The Genotype-Tissue Expression (GTEx) Project (tissue types, sample characteristics, data portal, eQTL networks, gene regulatory networks); multi-tissue transcriptome; public eQTL databases; transcriptome-wide association study (TWAS) Speaker: Max …

MGH Division of Clinical Research

A Practical Introduction to Statistical Genetics: Genome-Wide Association Studies (I)

Topics: GWAS history; genotyping technology; linkage disequilibrium, haplotype and tagging genetic variation; study design and statistical power; population stratification; marker quality control (marker call rate, minor allele frequency, Hardy-Weinberg equilibrium, differential missingness between cases and controls, batch effect); sample quality …

MGH Division of Clinical Research

A Practical Introduction to Statistical Genetics: Genome-Wide Association Studies (II)

Topics: association analysis (regression, effect size and odds ratio, hypothesis testing, type I and type II errors); visualization and diagnosis (Manhattan plot, LocusZoom, population stratification, spurious association); GWAS summary statistics; meta-analysis; functional annotation and gene-set/pathway analysis; introduction to mixed effects …

MGH Division of Clinical Research

A Practical Introduction to Statistical Genetics: Mendelian Randomization (MR)

Topics: causal effects and graphical representation; instrumental variables; basic ideas, advantages, assumptions and caveats of MR; two-stage least square method for MR; ratio of coefficient method for MR; MR using multiple SNPs; MR using GWAS summary statistics; two-sample MR; detecting …

MGH Division of Clinical Research

A Practical Introduction to Statistical Genetics: Statistical Fine-Mapping

Topics: goal of statistical fine-mapping; partitioning and interpreting GWAS lead signals; factors influencing fine-mapping (sample size, number of causal SNPs, effect sizes of causal SNPs, local LD structure, SNP density); statistical methods and software (heuristic methods, penalized regression, Bayesian methods); …