Incorporation of DNA methylation quantitative trait loci (mQTLs) in epigenome-wide association analysis: application to birthweight effects in neonatal whole blood

Li, Shaobo; Mancuso, Nicholas; Metayer, Catherine; Ma, Xiaomei; Smith, Adam J. de

doi:10.1186/s13148-022-01385-6

Cited by 3 publications

(1 citation statement)

References 52 publications

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“…Single nucleotide polymorphisms (SNPs) associated with DNAm are known as methylation quantitative trait loci (meQTLs) [ 19 – 22 ], which represent the interplay between the genome and the methylome. In recent years, genome-wide meQTL mapping has been conducted to deepen our understanding of the mechanisms of cardiovascular disease [ 23 ], smoking [ 24 ],, schizophrenia [ 25 ], and birthweight [ 26 ] However, meQTLs have not been explicitly examined for CU-associated DNAm loci and their potential role in the comorbidities linked to CU.…”

Section: Introductionmentioning

confidence: 99%

Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits

Cheng,

Justice,

Wang

et al. 2023

BMC Genomics

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Background Cocaine use (CU) is associated with psychiatric and medical diseases. Little is known about the mechanisms of CU-related comorbidities. Findings from preclinical and clinical studies have suggested that CU is associated with aberrant DNA methylation (DNAm) that may be influenced by genetic variants [i.e., methylation quantitative trait loci (meQTLs)]. In this study, we mapped cis-meQTLs for CU-associated DNAm sites (CpGs) in an HIV-positive cohort (Ntotal = 811) and extended the meQTLs to multiple traits. Results We conducted cis-meQTL analysis for 224 candidate CpGs selected for their association with CU in blood. We identified 7,101 significant meQTLs [false discovery rate (FDR) < 0.05], which mostly mapped to genes involved in immunological functions and were enriched in immune pathways. We followed up the meQTLs using phenome-wide association study and trait enrichment analyses, which revealed 9 significant traits. We tested for causal effects of CU on these 9 traits using Mendelian Randomization and found evidence that CU plays a causal role in increasing hypertension (p-value = 2.35E-08) and decreasing heel bone mineral density (p-value = 1.92E-19). Conclusions These findings suggest that genetic variants for CU-associated DNAm have pleiotropic effects on other relevant traits and provide new insights into the causal relationships between cocaine use and these complex traits.

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Section: Introductionmentioning

confidence: 99%

Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits

Cheng,

Justice,

Wang

et al. 2023

BMC Genomics

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Methylation and expression quantitative trait loci rs1799971 in the OPRM1 gene and rs4654327 in the OPRD1 gene are associated with opioid use disorder

Yu,

Zhang,

Xun

et al. 2023

Neuroscience Letters

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Gene–Environment Analyses Reveal Novel Genetic Candidates with Prenatal Tobacco Exposure in Relation to Risk for Childhood Acute Lymphoblastic Leukemia

Zhong,

Li,

Arroyo

et al. 2023

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background. Associations between maternal tobacco exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL) have yielded mixed results. This may be due to biases in self-reported smoking or other differences in individual level risk factors. We utilized a biological marker of maternal tobacco exposure to evaluate the association between maternal tobacco exposure during pregnancy, genetics, and subsequent childhood ALL risk in two large population-based studies of childhood ALL in California. Methods. Maternal exposure to tobacco smoke was assessed with a validated methylation marker (cg05575921) of the aryl hydrocarbon receptor repressor (AHRR) gene in newborn dried blood spots. We adjusted for sex, birthweight, gestational age, mode of delivery, year of birth, AHRR quantitative trait locus (mQTL) rs77111113, and a polygenetic risk score for childhood ALL. We additionally adjusted for principal components in a gene-environment interaction testing method that incorporates gene-only and environment-only effects along with interactions. Results. AHRR hypomethylation overall was not associated with childhood ALL. In gene-environment interaction testing, several genetic variants displayed significant interaction with AHRR hypomethylation and childhood ALL. Conclusions. Our results suggest novel candidates in PTPRK and DPP6 may play a role in tobacco-related leukemogenesis. Further research is necessary to better understand the effects of tobacco and these variants on childhood ALL risk. Impact: Despite lack of an overall “main effect,” tobacco exposure during pregnancy impacts childhood ALL risk depending on specific genetic variants.

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Incorporation of DNA methylation quantitative trait loci (mQTLs) in epigenome-wide association analysis: application to birthweight effects in neonatal whole blood

Cited by 3 publications

References 52 publications

Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits

Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits

Methylation and expression quantitative trait loci rs1799971 in the OPRM1 gene and rs4654327 in the OPRD1 gene are associated with opioid use disorder

Gene–Environment Analyses Reveal Novel Genetic Candidates with Prenatal Tobacco Exposure in Relation to Risk for Childhood Acute Lymphoblastic Leukemia

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