Veijola, J. | Search bioRxiv

bioRxiv2018

DNA methylation links prenatal smoking exposure to later life health outcomes in offspring.

Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. To test this, we examined the association of prenatal maternal smoking with DNA methylation in 2,821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess, whether methylation markers have causal effects on disease outcomes in the offspring. We identify 69 differentially methylated CpGs in 36 genomic regions (P < 1x10-7), and show that DNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.

epidemiology↗

bioRxiv2017

Polygenic risk scores applied to a single cohort reveal pleiotropy among hundreds of human phenotypes

BackgroundThere is now convincing evidence that pleiotropy across the genome contributes to the correlation between human traits and comorbidity of diseases. The recent availability of genome-wide association study (GWAS) results have made the polygenic risk score (PRS) approach a powerful way to perform genetic prediction and identify genetic overlap among phenotypes.\n\nMethods and findingsHere we use the PRS method to assess evidence for shared genetic aetiology across hundreds of traits within a single epidemiological study - the Northern Finland Birth Cohort 1966 (NFBC1966). We replicate numerous recent findings, such as a genetic association between Alzheimers disease and lipid levels, while the depth of phenotyping in the NFBC1966 highlights a range of novel significant genetic associations between traits.\n\nConclusionsThis study illustrates the power in taking a hypothesis-free approach to the study of shared genetic aetiology between human traits and diseases. It also demonstrates the potential of the PRS method to provide important biological insights using only a single well-phenotyped epidemiological study of moderate sample size (~5k), with important advantages over evaluating genetic correlations from GWAS summary statistics only.

genetics↗