.Conclusions We applied a novel implementation of bioinformatics tools to collapse person CpG outcomes to a gene score and performed pathway analysis to test for in utero epigenetic changes by maternal smoking in 1062 participants within the MoBa. By collapsing individual CpG effects to gene scores, we discovered substantial differential methylation in 15 genes (q0.25), nine of which were not detected by only testing person CpGs. Moreover, pathway analysis revealed considerable associations with 51 pathways, 32 of which replicated in an independent cohort of 685 participants. Significantly associated pathways, that replicated inside the independent cohort, represent diverse biological processes which includes cancer, cell cycle, ER receptor signaling,Rotroff et al. BMC Genomics (2016) 17:Web page 11 ofUSA. 4Norwegian Institute of Public Wellness, Oslo, Norway. 5Public Overall health Sciences Division, Fred Hutchinson Cancer Study Center, Seattle, WA, USA. 6 Centre for Clinical Investigation, Haukeland University Hospital, Bergen, Norway. 7 Department of Clinical Science, University of Bergen, Bergen, Norway. 8 Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway. 9Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, USA. Received: 9 February 2016 Accepted: 17 November21.22. 23.24. References 1. Overall health UD of, Solutions H, et al. The wellness consequences of involuntary exposure to tobacco smoke: a report on the Surgeon Basic. Atlanta: US Department of Overall health and Human Services, Centers for Disease Control and Prevention. Coord. Cent. Overall health Promot. Natl. Cent. Chronic Dis. Prev. Health Promot. Off. Smok. Wellness; 2006. p. 1988002. 2. Bhattacharya S, Beasley M, Pang D, Macfarlane GJ. Maternal and perinatal threat aspects for childhood cancer: record linkage study.Lipocalin-2/NGAL Protein Species BMJ Open. 2014;4: e003656. 3. Joubert BR, Haberg SE, Nilsen RM, Wang X, Vollset SE, Murphy SK, et al. 450 K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking throughout Pregnancy. Environ Overall health Perspect. 2012;120:14251. four. Lee KWK, Richmond R, Hu P, French L, Shin J, Bourdon C, et al.LAIR1 Protein Biological Activity Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenomewide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age.PMID:23537004 Environ Wellness Perspect. 2015;123:193. 5. Richmond RC, Simpkin AJ, Woodward G, Gaunt TR, Lyttleton O, McArdle WL, et al. Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC). Hum Mol Genet. 2015;24:22017. six. Markunas CA, Xu Z, Harlid S, Wade PA, Lie RT, Taylor JA, et al. Identification of DNA methylation adjustments in newborns related to maternal smoking throughout pregnancy. Environ Health Perspect. 2014;122:11473. 7. McRae AF, Powell JE, Henders AK, Bowdler L, Hemani G, Shah S, et al. Contribution of genetic variation to transgenerational inheritance of DNA methylation. Genome Biol. 2014;15:R73. 8. McCarthy MI, Hirschhorn JN. Genome-wide association studies: prospective subsequent actions on a genetic journey. Hum Mol Genet. 2008;17:R1565. 9. Sham Pc, Purcell SM. Statistical power and significance testing in large-scale genetic studies. Nat Rev Genet. 2014;15:3356. ten. Li M-X, Gui H-S, Kwan JSH, Sham Computer. GATES: A Speedy and Effective Gene-Based Association Test Making use of Extended Simes Procedure. Am J Hum Gen.
