From GWAS Hit to Mechanism: Trace a Disease Variant to the Enhancer, Gene, and Cell Type It Breaks

Isogenic Cell Lines and iPSC-Derived Models for Variant Testing Colocalization of GWAS and eQTL Signals CRISPR-Cas9 Mechanisms and Applications in Genome Editing Polygenic Risk Scores from GWAS Effect Sizes Bisulfite Sequencing and Methylation Arrays for CpG Methylation Single Nucleotide Polymorphisms and Common Human Genetic Variation Hidden Confounders in Expression Data and Latent Factor Correction Chromatin Remodeling Annotating Credible Set Variants by Overlap with Regulatory Elements Massively Parallel Reporter Assays for Testing Thousands of Variants Reading Regulatory Tracks in a Genome Browser at a GWAS Locus Batch Effect DNA Methylation Patterns Regulation of Gene Expression Lentiviral Delivery and Multiplicity of Infection in Pooled Screens Mapping Gene Distance in Centimorgans from Recombination Frequency in Genetics Coding versus Noncoding Variants and Where GWAS Hits Fall Heterogeneity Assessment Reading a Hi-C Contact Map: Compartments TADs and Loops Histone Modification Marks as Regulatory Element Signatures H3K27ac H3K4me1 H3K4me3 Enhancer Properties: Distance and Orientation Independence Modularity and Tissue Specificity Guide RNA Design Counting sgRNAs and Calling Screen Hits with MAGeCK CUT&RUN and CUT&Tag as Low-Input Alternatives to ChIP-seq Genome Coordinates Assembly Builds and Liftover between GRCh37 and GRCh38 Hi-C Chromatin Conformation Capture Stratified LD Score Regression: Partitioning Heritability across Annotations and Cell Types Variant Calling: From Bayesian Genotypers to DeepVariant Genotype Imputation from a Haplotype Reference Panel GWAS Quality Control: Call Rate Heterozygosity HWE and Sample Filters Interpreting p-Values and Significance Levels in Hypothesis Testing Enhancer-Promoter Communication by Looping Mediator and Cohesin Luciferase Reporter Assays for Enhancer Activity Allele and Haplotype Frequencies in Population Genetics Super-Enhancers and Cell Identity Genes Read Mapping to a Reference Genome Single-Cell ATAC-seq and Peak-by-Cell Matrices Peak Calling and Signal Normalization for Chromatin Sequencing Data Statistical Fine-Mapping: Posterior Inclusion Probabilities and Credible Sets Association Signal versus Causal Variant under Linkage Disequilibrium Genome-Wide Association Studies CRISPRi Tiling Screens across a GWAS Locus to Map Functional Enhancers Additive Genotype Coding as Allele Dosage 0 1 and 2 Tissue-Specific eQTLs and the GTEx Resource Nucleosomes and the Accessibility of DNA to Transcription Factors Haplotype Phasing Single-Cell Multiome: Joint RNA and ATAC from the Same Nucleus Fine-Mapping Pitfalls: LD Mismatch Imputation Quality and Allelic Heterogeneity Principal Component Analysis Single-Cell eQTLs and Cell-State-Dependent Genetic Effects Pooled Screen Readouts: Growth FACS Sorting on a Reporter and Sequencing Guides LD Score Regression for SNP Heritability and Confounding DNase-seq and Transcription Factor Footprinting Cell-Type-Specific Gene Expression from a Shared Genome Transcription Heritability Estimates SNP Genotyping Arrays and Tag SNP Selection Finding the Trait-Relevant Cell Type from Single-Cell Data and GWAS Summary Statistics Variant Consequence Annotation with Ensembl VEP Style Tools How a Noncoding Variant Changes Gene Expression: Motif Loss Gain and Chromatin Effects Population Stratification and Correction with Genotype Principal Components Topologically Associating Domains and CTCF Boundaries Hardy-Weinberg Equilibrium Linkage Disequilibrium: D Prime and r^2 between Nearby Variants Worked Locus: FTO Intronic Variants Act on IRX3 and IRX5 in Adipocyte Progenitors GWAS Summary Statistics and the LD Reference Panel Sum of Single Effects Fine-Mapping with Multiple Causal Variants Logistic Regression: Interpreting Odds Ratios via Exponentiated Coefficients LD Blocks Recombination Hotspots and Haplotype Structure Confounding Variables as Alternative Explanations for a Result Perturb-seq: Single-Cell Transcriptome Readout of Pooled Perturbations RNA-seq Quantification and Differential Expression Analyzing an MPRA: Barcode Counts Allelic Skew and Activity Calls Lead Variants Loci and Clumping a GWAS into Independent Signals Worked Locus: A 1p13 Variant Creates a C/EBP Site and Regulates SORT1 in Liver Allele-Specific Expression and Allelic Imbalance as Evidence of a Cis Effect The Central Dogma: DNA to Phenotype via Transcription and Translation Linking Peaks to Genes by Co-Variation across Single Cells Posterior Probability Histone Acetylation Promoter Capture Hi-C and HiChIP for Enhancer-Promoter Links Transcription Factors Introducing a Single Variant with Base Editing Prime Editing or HDR ChIP-seq for Transcription Factor and Histone Mark Occupancy Activity-by-Contact Models for Predicting Enhancer-Gene Links Single-Cell RNA-seq: From Count Matrix to Cell Types Expression Quantitative Trait Loci: Mapping Variants to Expression Levels Conditional and Joint Analysis for Multiple Signals at One Locus Chromatin State Segmentation from Combinations of Histone Marks Functionally Informed Fine-Mapping with Regulatory Annotation Priors Prime Editing CRISPR Activation and Interference for Gene Expression Regulation in Molecular Biology ENCODE Roadmap Epigenomics and Regulatory Annotation Atlases Multiple Hypothesis Testing Correction in Statistics Mouse Models of Human Regulatory Variants and Their Limits The GWAS Per-Variant Regression Test and Effect Size Designing a Pooled CRISPR Screen: Library Coverage and Controls Genome-Wide Significance and the 5 x 10^-8 Threshold Simple Linear Regression: Intercept, Slope, and Least-Squares Fitting Predicting Motif Disruption by a Noncoding Variant The VCF Format and Its Coordinate Assumption Motif Accessibility Deviation Scores across Single Cells Cis versus Trans eQTLs and the Distance Window ATAC-seq for Chromatin Accessibility Base Editing Why Many GWAS Loci Have No Matching eQTL Polygenic Architecture of Complex Traits and Missing Heritability Trans-Ancestry Fine-Mapping Using Differing LD Structures Winner's Curse and Replication of GWAS Associations Transcriptome-Wide Association and Mendelian Randomization for Gene-Level Causality From Mechanism to Drug Target: Genetic Support for Therapeutic Hypotheses Inferring an Enhancer-Driven Gene Regulatory Network from Multiome Data Validating Screen Hits with Individual Guides and Orthogonal Assays Combinatorial Transcription Factor Binding and Enhancer Grammar Minor Allele Frequency and Common versus Rare Variants Cell Type Annotation Epigenetic Memory: Maintaining Chromatin States through Cell Division Splicing Chromatin Accessibility and Methylation QTLs Silencing an Enhancer with dCas9-KRAB CRISPR Interference Variant Effect Prediction with Genomic Foundation Models Pioneer Transcription Factors and Opening Closed Chromatin Cis-Regulatory Elements: Promoters Enhancers Silencers and Insulators Tracing a GWAS Variant to the Enhancer Gene and Cell Type It Breaks Reading Manhattan and Q-Q Plots from a GWAS Next-Generation Sequencing Enhancers & Transcription Factors Linear Mixed Models and Genetic Relatedness in Association Testing Gene Regulatory Network Inference False Discovery Rate Control with Benjamini-Hochberg Transcription Factor Binding Motifs and Position Weight Matrices Which Gene an Enhancer Regulates and the Nearest-Gene Fallacy Knock-In by Homology-Directed Repair EMSA and Allele-Specific ChIP for Differential Transcription Factor Binding GWAS Meta-Analysis and Heterogeneity across Cohorts Weighing Lines of Evidence for a Causal Gene at a GWAS Locus