Reply to: Genetic differentiation at probe SNPs leads to spurious results in meQTL discovery
Year: 2023
Type: letter
Abstract: In the paper by Li et al. 1 , we reported DNA methylation (DNAm) of 946 CpG sites influenced by genetic variants in the conventional model (LA-naïve), and 135 CpGs with genetic effects that significantly differed by local ancestry (LA-specific). Meeks et al. raised a concern that 37.5% of the 946 CpG sites were inadequately controlled as they contained nearby commons variants (Probe-SNPs). They argued that different allele frequencies of probe-SNP between populations of African ancestry and European ancestry led to spurious findings in the paper. In response to Meeks et al.’s concern, using a Methyl-Seq approach in a subset of the samples (N = 211), we were able to show that a large proportion (47.1%-71.6%) of the significant SNP-CpG associations originally reported by Li et al. using Illumina HumanMethylation 450K (HM450K) 1 were replicated. We did not observe significant difference in the replication rates between CpGs with and without probe-SNPs, indicating that there is no substantial evidence to suggest that CpGs with probe-SNPs biased our published findings.
Source: Communications Biology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,690
Awards: G1044130170, G1158786059, G1371745463, 4/6 COMpAAAS U01: Operations Research Study, Using the VACS Index to track health outcomes associated with changes in drug use, G2321611145, G2358688911, G2364989932, G2615631298, Feature selection of DNA methylation biosignatures for neuropathy with comorbid drug abuse in the setting of HIV infection, Defining the impact of injection drug use on antiretroviral therapy and HIV treatment outcomes: an (epi)genomic approach, G3673658808, G456027550, Genome-wide DNA methylation in HIV infected drug users, G4978770116, G513759803, G5416541439, G5995332565, G6520187845, G679121021, Enhancing Discovery of HIV Host Genetics using Drug Abuse and other Interactions, G9000095569, G9000156273, G9000172886, Yale Clinical and Translational Science Award
OpenAlex ID: W4390059832