DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan
van IJzendoorn Marinus H.; Suderman Matthew; Baselmans Bart M. L.; Bakermans-Kranenburg Marian J.; Snieder Harold; Jarvelin Marjo-Riitta; Lehtimäki Terho; Lahti Jari; Konrad Kerstin; Corpeleijn Eva; Vuoksimaa Eero; Witt Stephanie H.; Franke Lude; Streit Fabian; Keltikangas-Järvinen Liisa; Strandberg Timo; Frank Josef; van Dongen Jenny; Morris Stewart W.; Hannon Eilis; Caspi Avshalom; Franke Barbara; Hervas Amaia; Adams Mark J.; McIntosh Andrew M.; Sebert Sylvain; Evandt Jorunn; Tiemeier Henning; Hakulinen Christian; Sugden Karen; Vermeiren Robert; Felix Janine F.; Ligthart Lannie; Hafferty Jonathan D.; Boomsma Dorret I.; Kaprio Jaakko; Hagenbeek Fiona A.; Relton Caroline; Moffitt Terrie E.; Davies Gareth E.; Evans Kathryn L.; Freitag Christine M.; Chiocchetti Andreas G.; Kluft Cornelis; Sirignano Lea; Consortium BIOS; Wang Yunzhang; Poulton Richie; Meijer Mandy; Mishra Pashupati Prasad; Mulder Rosa H.; Roetman Peter J.; Walker Rosie M.; Lowry Estelle; Ip Hill F.; Pedersen Nancy L.; Vetro Agnes; Arseneault Louise; Küpers Leanne K.; Jansen Rick; Gutzkow Kristine B.; Hägg Sara; Vrijheid Martine; Korhonen Tellervo; Gonzalez Juan R.; Jylhävä Juulia; Colins Olivier F.; Raitakari Olli; van der Meer Dennis; Binder Elisabeth; Bartels Meike; Czamara Darina; Ollikainen Miina; Escaramis Georgia; Mill Jonathan; Bonder Marc Jan; Sunyer Jordi; Deuschle Michael; Parmar Priyanka; Alemany Silvia; Vafeiadi Marina; Klein Marieke; Corcoran David L.; Ismail Khadeeja; Fernández-Rivas Aranzazu; Räikkönen Katri; Send Tabea S.; Grazuleviciene Regina; Campbell Archie
https://urn.fi/URN:NBN:fi-fe2021093048206
Tiivistelmä
DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10-7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
Kokoelmat
- Rinnakkaistallenteet [19207]