A multivariant recall-by-genotype study of the metabolomic signature of BMI.

OBJECTIVE: This study estimated the effect of BMI on circulating metabolites in young adults using a recall-by-genotype study design. METHODS: A recall-by-genotype study was implemented in the Avon Longitudinal Study of Parents and Children. Samples from 756 participants were selected for untargeted metabolomics analysis based on low versus high genetic liability for higher BMI defined by a genetic risk score (GRS). Regression analyses were performed to investigate associations between BMI GRS group and relative abundance of 973 metabolites. RESULTS: After correction for multiple testing, 29 metabolites were associated with BMI GRS group. Bilirubin was among the most strongly associated metabolites, with reduced levels measured in individuals in the high-BMI GRS group (ß = -0.32, 95% CI: -0.46 to -0.18, Benjamini-Hochberg adjusted p = 0.005). This study observed associations between BMI GRS group and the levels of several potentially diet-related metabolites, including hippurate, which had lower mean abundance in individuals in the high-BMI GRS group (ß = -0.29, 95% CI: -0.44 to -0.15, Benjamini-Hochberg adjusted p = 0.008). CONCLUSIONS: Together with existing literature, these results suggest that a genetic predisposition to higher BMI captures differences in metabolism leading to adiposity gain. In the absence of prospective data, separating these effects from the downstream consequences of weight gain is challenging.

The impact of low input DNA on the reliability of DNA methylation as measured by the Illumina Infinium MethylationEPIC BeadChip.

DNA methylation (DNAm) is commonly assayed using the Illumina Infinium MethylationEPIC BeadChip, but there is currently little published evidence to define the lower limits of the amount of DNA that can be used whilst preserving data quality. Such evidence is valuable for analyses utilizing precious or limited DNA sources. We used a single pooled sample of DNA in quadruplicate at three dilutions to define replicability and noise, and an independent population dataset of 328 individuals (from a community-based study including US-born non-Hispanic Black and white persons) to assess the impact of total DNA input on the quality of data generated using the Illumina Infinium MethylationEPIC BeadChip. We found that data are less reliable and more noisy as DNA input decreases to 40ng, with clear reductions in data quality; and that low DNA input is associated with a reduction in power to detect EWAS associations, requiring larger sample sizes. We conclude that DNA input as low as 40ng can be used with the Illumina Infinium MethylationEPIC BeadChip, provided quality checks and sensitivity analyses are undertaken.

Longitudinal serological measures of common infection in the Avon Longitudinal Study of Parents and Children cohort.

Antibodies against pathogens provide information on exposure to infectious agents and are meaningful measures of past and present infection. Antibodies were measured in the plasma of children that are the offspring in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Plasma was collected during clinics at age 5, 7, 11 and 15 years. The antigens examined include: fungal ( Saccharomyces cerevisiae); protozoan ( Toxoplasma gondii and surface antigen 1 of  T. gondii); herpes viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1); common colds (influenza virus subtypes H1N1 and H3N2); other antigens (measles); animal (feline herpes virus, Theiler's virus); bacteria ( Helicobacter pylori); dietary antigens (bovine casein alpha protein, bovine casein beta protein). Alongside the depth of data available within the ALSPAC cohort, this longitudinal resource will enable the investigation of the association between infections and a wide variety of outcomes.