# Serum microRNA expression quantitative trait loci in children with asthma colocalize with asthma-related GWAS results

## TL;DR

This study finds genetic links to microRNA expression in children with asthma that overlap with known asthma risk genes.

## Contribution

Identifies novel miRNA-QTLs in asthma and shows their overlap with asthma-related GWAS results.

## Key findings

- 28 significant cis-miRNA-QTL associations were identified, 12 of which are novel.
- Three novel miRNA-QTLs were replicated in an independent cohort.
- The QTLs overlap with asthma-related GWAS hits and tissue-specific expression QTLs.

## Abstract

Asthma poses a significant public health burden. Despite identifying more than a hundred genetic risk loci in genome-wide association studies (GWAS), the underlying functional mechanisms remain poorly understood. Studying omics, especially microRNAs (miRNAs), is a promising approach to facilitate our understanding of the biological pathways of asthma. Here, we performed miRNA expression quantitative trait loci (miRNA-QTL) analyses using whole-genome sequencing and serum-based miRNA expression data from two independent cohorts of children with asthma (Genetic Epidemiology of Asthma in Costa Rica Study (GACRS), (NCT00021840, 2005-06-23) (N = 980, Discovery) and the Childhood Asthma Management Program (CAMP) (NCT00000575, 2005-06-23) (N = 354, Replication)). Our robust discovery analysis identified 28 significant cis-miRNA-QTL associations, where 12 were not reported in three independent miRNA-QTL studies. Three of these 12 signals were replicated in CAMP. The QTLs colocalize with expression and splicing QTL in asthma-relevant tissues and cells, and overlap with asthma-related and blood cell trait GWAS hits.