Comprehensive evaluation of smoking exposures and their interactions on DNA methylation

This is the author accepted manuscript.Data Sharing Statement: Data from the Norwegian Mother, Father and Child Cohort Study and the Medical Birth Registry of Norway used in this study are managed by the national health register holders in Norway (Norwegian Institute of public health) and can be made available to researchers, provided approval from the Regional Committees for Medical and Health Research Ethics (REC), compliance with the EU General Data Protection Regulation (GDPR) and approval from the data owners. The consent given by the participants does not open for storage of data on an individual level in repositories or journals. Researchers who want access to data sets for replication should apply through helsedata.no. Access to data sets requires approval from The Regional Committee for Medical and Health Research Ethics in Norway and an agreement with MoBa. Access to the START data is available upon application to the Norwegian Institute of Public Health (NIPH). An application form in English can be found at the NIPH website (http://www.fhi.no/en/). Questions regarding the START cohort can be directed to Siri Håberg ([email protected]). Access to the ALHS is available upon request through the Agricultural Health Study Executive committee. Interested parties will need to complete a data transfer agreement with NIEHS. Questions about the ALHS can be directed to Stephanie London ([email protected]). According to the terms of consent for GS participants, access to individual-level data (omics and phenotypes) must be reviewed by the GS Access Committee. Applications should be made to [email protected]. Guidance on the Generation Scotland Access Process and Policy can be found here: https://www.ed.ac.uk/generation-scotland/using-resources/access-to-resources Understanding Society data are available through the UK Data Service (https://ukdataservice.ac.uk/). Access to the Biobank-Based Integrative Omics Studies (BIOS) is available upon request. RNA-seq, DNA methylation, sex, age and cell count data can be requested and downloaded from the European Genome-phenome Archive (EGA), accession EGAS00001001077. An application form in English can be found at the BBMRI website: https://www.bbmri.nl/acquisition-use-analyze/biosBackground: Smoking impacts DNA methylation, but data are lacking on smoking-related differential methylation by sex or dietary intake, recent smoking cessation (<1 year), persistence of differential methylation from in utero smoking exposure, and effects of environmental tobacco smoke (ETS). Methods: We meta-analysed data from up to 15,014 adults across 5 cohorts with DNA methylation measured in blood using Illumina’s EPIC array for current smoking (2,560 exposed), quit <1 year (500 exposed), in utero (286 exposed), and ETS exposure (676 exposed). We also evaluated the interaction of current smoking with sex or diet (fibre, folate, and vitamin C). Findings: Using false discovery rate (FDR<0.05), 65,857 CpGs were differentially methylated in relation to current smoking, 4,025 with recent quitting, 594 with in utero exposure, and 6 with ETS. Most current smoking CpGs attenuated within a year of quitting. CpGs related to in utero exposure in adults were enriched for those previously observed in newborns. Differential methylation by current smoking at 4-71 CpGs may be modified by sex or dietary intake. Nearly half (35-50%) of differentially methylated CpGs on the 450K array were associated with blood gene expression. Current smoking and in utero smoking CpGs implicated 3,049 and 1,067 druggable targets, including chemotherapy drugs. Interpretation: Many smoking-related methylation sites were identified with Illumina’s EPIC array. Most signals revert to levels observed in never smokers within a year of cessation. Many in utero smoking CpGs persist into adulthood. Smoking-related druggable targets may provide insights into cancer treatment response and shared mechanisms across smoking-related diseases.Norwegian Ministry of Health and Care ServicesMinistry of Education and ResearchResearch Council of NorwayNational Institutes of Health, National Institute of Environmental Health SciencesNational Cancer Institut

Genetic studies of body mass index yield new insights for obesity biology

Based on fieldwork in Trento, Italy, this paper investigates the process of playlisting in three commercial radio stations, illustrating the implicit and explicit norms that define this process. I call special attention to DJs and their activity of mediation between music makers and their audience – an activity that includes the choice and the manipulation of musical material for precise communicative goals. It is my aim to show how the definition of what is appropriate for the playlist, which I define as “playlist value”, is subject to different kinds of constraints. Among these, on the one hand we find more pressing structural restrictions from advertisers, music labels and functional features of the radio; on the other hand, we find less urgent, and yet just as effective cultural constraints, that push DJs to adjust their playlists to those of national network

Genetic studies of body mass index yield new insights for obesity biology

Note: A full list of authors and affiliations appears at the end of the article. Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p