Co-occurring expression and methylation QTLs allow detection of common causal variants and shared biological mechanisms

• Published in: Nature communications Vol. 9; no. 1; pp. 804 - 12
• Main Authors: Pierce, Brandon L., Tong, Lin, Argos, Maria, Demanelis, Kathryn, Jasmine, Farzana, Rakibuz-Zaman, Muhammad, Sarwar, Golam, Islam, Md. Tariqul, Shahriar, Hasan, Islam, Tariqul, Rahman, Mahfuzar, Yunus, Md, Kibriya, Muhammad G., Chen, Lin S., Ahsan, Habibul
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.02.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 38/22; 38/61; 45/43; 631/208/176/1988; 631/208/177; 631/208/200; 631/208/480; Adult; Bangladesh; Correlation analysis; Deoxyribonucleic acid; DNA; DNA Methylation; Female; Gene Expression; Gene loci; Gene mapping; Genetic diversity; Genetic Variation; Genome, Human; Genome-Wide Association Study; Genomes; Genomics; Humanities and Social Sciences; Humans; Identification methods; Localization; Male; Middle Aged; multidisciplinary; Peripheral blood; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Regulatory mechanisms (biology); Ribonucleic acid; RNA; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03209-9

Inherited genetic variation affects local gene expression and DNA methylation in humans. Most expression quantitative trait loci ( cis -eQTLs) occur at the same genomic location as a methylation QTL ( cis -meQTL), suggesting a common causal variant and shared mechanism. Using DNA and RNA from peripheral blood of Bangladeshi individuals, here we use co-localization methods to identify eQTL-meQTL pairs likely to share a causal variant. We use partial correlation and mediation analyses to identify >400 of these pairs showing evidence of a causal relationship between expression and methylation (i.e., shared mechanism) with many additional pairs we are underpowered to detect. These co-localized pairs are enriched for SNPs showing opposite associations with expression and methylation, although many SNPs affect multiple CpGs in opposite directions. This work demonstrates the pervasiveness of co-regulated expression and methylation in the human genome. Applying this approach to other types of molecular QTLs can enhance our understanding of regulatory mechanisms. Most expression QTLs (eQTLs) co-occur with a DNA methylation QTL (meQTL), suggesting a common causal variant. Here the authors analyse DNA and RNA from blood and identify eQTL-meQTL pairs likely to share a causal variant, finding that expression and methylation are often genetically co-regulated.