Genetic correlation-guided mega-analysis of DO mice provides mechanistic insight and candidate genes for age-related pathologies

Diversity Outbred (DO) mice are a powerful model system for mapping complex traits due to their high genetic diversity and mapping resolution. However, while there are extensive tools available for standard genetic analysis in DO mice, fewer techniques have been implemented to facilitate integrated, cross-study analysis. Here, we implement Haseman-Elston regression to estimate genetic correlations among 7,233 phenotypes measured across eleven independent DO mouse studies.  We used this network of genetic correlations to cluster phenotypes according to shared genetics, which enhanced the power to detect quantitative trait loci (QTL). This approach empowered the detection of 884 QTL for 383 meta-phenotypes, explaining an average of 40.36% of the total genetic variance per mega-analysis. We leveraged this network for insights into specific areas of biology, including lifespan, frailty, immune composition, histological and functional lung phenotypes, and histological phenotypes of..., , # Genetic correlation-guided mega-analysis of DO mice provides mechanistic insight and candidate genes for age-related pathologies

Dataset DOI: [10.5061/dryad.sj3tx96gd](10.5061/dryad.sj3tx96gd)

## Description of the data and file structure

The data in this repo correspond to a genetic analysis of Diversity Outbred (DO) mice conducted using internal data collected by Calico Life Sciences LLC and publicly available DO mouse datasets. This involved unifying several previously generated datasets, each of which involved distinct experimental efforts, for mega-analysis.

### Files and variables

#### File: Table_S1_DO_Phenotypes_normalized.csv

**Description:** Contains Mouse IDs, covariates used in phenotype processing, and z-score normalized phenotype values. ‘Mouse_ID’ is a unique identifier corresponding to each unique animal and includes study information. ‘Age’ is a covariate corresponding to the age of each animal at the time of phenotyping. For certain animals, different phenotyp...,