--- title: "Single-trait Fine-mapping with FineBoost" output: rmarkdown::html_vignette vignette: > %\VignetteIndexEntry{Single-trait Fine-mapping with FineBoost} %\VignetteEngine{knitr::rmarkdown} %\VignetteEncoding{UTF-8} --- ```{r, include = FALSE} knitr::opts_chunk$set( collapse = TRUE, comment = "#>", dpi = 50 ) ``` This vignette demonstrates how to perform single-trait fine-mapping analysis using FineBoost, a specialized single-trait version of ColocBoost, with both individual-level data and summary statistics. Specifically focusing on the 2nd trait with 2 causal variants (194 and 589) from the `Ind_5traits` and `Sumstat_5traits` datasets included in the package. ```{r setup} library(colocboost) ``` # 1. Fine-mapping with individual-level data In this section, we demonstrate how to perform fine-mapping using individual-level genotype (`X`) and phenotype (`Y`) data. This approach uses raw data directly to identify causal variants. ```{r load-example-individual} # Load example data data(Ind_5traits) X <- Ind_5traits$X[[2]] Y <- Ind_5traits$Y[[2]] res <- colocboost(X = X, Y = Y) colocboost_plot(res) ``` # 2. Fine-mapping with summary statistics This section demonstrates fine-mapping analysis using summary statistics along with a proper LD matrix. ```{r load-example-sumstat} # Load example data data(Sumstat_5traits) sumstat <- Sumstat_5traits$sumstat[[2]] LD <- get_cormat(Ind_5traits$X[[2]]) res <- colocboost(sumstat = sumstat, LD = LD) colocboost_plot(res) ``` # 3. LD-free fine-mapping with one causal variant assumption In scenarios where LD information is unavailable, FineBoost can still perform fine-mapping under the assumption that there is a single causal variant. This approach is less computationally intensive but assumes that only one variant within a region is causal. ```{r ld-free} # Load example data res <- colocboost(sumstat = sumstat) colocboost_plot(res) ``` **Note**: Weak learners SEL in FineBoost may capture noise as putative signals, potentially introducing false positives to our findings. To identify and filter spurious signals, we discard fine-tunned the threshold of $\Delta L_l$ using extensive simulations to balance sensitivity and specificity. This threshold is set to 0.025 by default for ColocBoost when detect the colocalization, but we suggested a less conservative threshold of 0.015 for FineBoost when performing single-trait fine-mapping analysis (`check_null_max = 0.015` as we suggested).