Most Recent Articles: Clinical Epigenetics

Most Recent Articles: Clinical Epigenetics

Full size table Epigenome-wide association study of childhood liver fat accumulation We assessed associations of DNA methylation in cord blood and in whole peripheral blood at 10 years with liver fat as a continuous measure in 10-year-old children. In the main models, adjusted for maternal age, education level, early-pregnancy BMI and smoking, gestational age at birth (cord blood analyses) or child age (childhood analyses), child sex, cell-type proportions, and batch, we did not observe any CpGs at birth or at 10 years to be associated with liver fat accumulation at 10 years after Bonferroni ( p value  95% per sample were processed further. Probes on the X and Y chromosomes were excluded from the analyses. The final datasets contained 457,774 probes in the newborn dataset and 458,563 probes in the 10-year-old dataset. For all CpGs and differentially methylated regions, the official gene name of the nearest gene was noted using Illumina’s annotation information and we enhanced the annotation provided by Illumina with the UCSC Genome Browser build hg19 [ 27 , 28 ]. Liver fat fraction at 10 years We measured liver fat using a 3.0 Tesla MRI (Discovery MR750w, GE Healthcare, Milwaukee, WI, USA) [ 1 , 22 , 23 , 24 ]. The children wore light clothing without metal objects while undergoing the body scan. A liver fat scan was performed using a single-breath-hold, 3D volume and a special 3-point proton density-weighted Dixon technique (IDEAL IQ) for generating a precise liver fat fraction image [ 29 ]. The IDEAL IQ scan is based on a carefully tuned 6-echo echo-planar imaging acquisition. The obtained fat-fraction maps were subsequently analyzed by the Precision Image Analysis (PIA, Kirkland, WA, USA) using the sliceOmatic (TomoVision, Magog, QC, CAN) software package. All extraneous structures and any image artifacts were removed manually [ 30 ]. The liver fat fraction was measured independent of any outcome, determined by taking four samples of at least 4 cm 2 from the central portion of the hepatic volume. Subsequently, the mean signal intensities were averaged to generate an overall mean liver fat fraction estimation. Liver fat fraction measured with IDEAL IQ using MRI is reproducible, highly precise, and validated in adults [ 31 , 32 ]. As previously described, non-alcoholic fatty liver disease was defined as liver fat fraction ≥ 5.0% [ 1 , 32 , 33 ]. We studied liver fat accumulation across the full spectrum as our primary objective. As the secondary objective, we dichotomized liver fat into low, ≤ 2.0%, and high, > 2.0%, liver fat accumulation. This cutoff was based on the median in our population and on previous work from our group describing that liver fat accumulation above 2.0% is already associated with an increased cardio-metabolic risk profile in children [ 34 ]. Due to the lower numbers of cases, we could not dichotomize liver fat accumulation based on the clinical cutoff of ≥ 5.0%. Covariates At enrolment in the study, information on maternal age and educational level was obtained by questionnaires. Maternal smoking during pregnancy was assessed by questionnaires in pregnancy. We measured maternal height and weight at enrolment to calculate early-pregnancy BMI [ 35 ]. Information on gestational age at birth, child sex, and age at 10 years visit was obtained from medical records. We measured height and weight in the children, without shoes and heavy clothing. Childhood BMI was calculated and sex- and age-adjusted childhood BMI standard deviation scores were calculated (Growth Analyzer 4.0, Dutch Growth Research Foundation) [ 36 ]. Look-up study of adult CpGs associated with liver fat We examined in our data the associations of the 22 CpGs known from previous literature to be associated with liver fat accumulation in adults with liver fat accumulation in children [ 6 ]. A Bonferroni corrected p value