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Preliminary Communication

Leukocyte Methylomic Imprints of Exposure to the Genocide against the Tutsi in Rwanda: a Pilot Epigenome-Wide Analysis

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Pages 11-25 | Received 14 Aug 2021, Accepted 01 Nov 2021, Published online: 08 Dec 2021

References

  • Lowe SR , JoshiS , GaleaSet al. Pathways from assaultive violence to post-traumatic stress, depression, and generalized anxiety symptoms through stressful life events: longitudinal mediation models. Psychol. Med.47(14), 2556–2566 (2017).
  • Kubzansky LD , KoenenKC , JonesCet al. A prospective study of posttraumatic stress disorder symptoms and coronary heart disease in women. Health Psychol.28(1), 125–130 (2009).
  • Kubzansky LD , KoenenKC , SpiroAIIIet al. Prospective study of posttraumatic stress disorder symptoms and coronary heart disease in the Normative Aging Study. Arch. Gen. Psychiatry64(1), 109–116 (2007).
  • Keyes KM , McLaughlinKA , DemmerRTet al. Potentially traumatic events and the risk of six physical health conditions in a population-based sample. Depress. Anxiety30(5), 451–460 (2013).
  • Husarewycz MN , GabalawyREI , LogsettySet al. The association between number and type of traumatic life experiences and physical conditions in a nationally representative sample. Gen. Hosp. Psychiatry36(1), 26–32 (2014).
  • Jawaid A , RoszkowskiM , MansuyIMet al. Transgenerational epigenetics of traumatic stress. Prog. Mol. Biol. Transl. Sci.158, 273–298 (2018).
  • Babenko O , KovalchukI , MetzGAet al. Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health. Neurosci. Biobehav. Rev.48, 70–91 (2015).
  • Ulloa AC , GligaA , LoveTMet al. Prenatal methylmercury exposure and DNA methylation in seven-year-old children in the Seychelles Child Development Study. Environ. Int.147, 106321 (2021).
  • Park J , KimJ , KimEet al. Prenatal lead exposure and cord blood DNA methylation in the Korean Exposome Study. Environ. Res.195, 110767 (2021).
  • del Blanco B , BarcoA. Impact of environmental conditions and chemicals on the neuronal epigenome. Curr. Opin. Chem. Biol.45, 157–165 (2018).
  • Serpeloni F , RadtkeKM , HeckerTet al. Does prenatal stress shape postnatal resilience? – An epigenome-wide study on violence and mental health in humans. Front. Genet.10, 269 (2019).
  • Sosnowski DW , BoothC , YorkTPet al. Maternal prenatal stress and infant DNA methylation: a systematic review. Dev. Psychobiol.60(2), 127–139 (2018).
  • Bowers ME , YehudaR. Intergenerational transmission of stress in humans. Neuropsychopharmacology41(1), 232–244 (2016).
  • Mulligan CJ , D’ErricoNC , SteesJet al. Methylation changes at NR3C1 in newborns associate with maternal prenatal stress exposure and newborn birth weight. Epigenetics7(8), 853–857 (2012).
  • Yehuda R , LehrnerA. Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms. World Psychiatry17(3), 243–257 (2018).
  • Kertes DA , KaminHS , HughesDAet al. Prenatal maternal stress predicts methylation of genes regulating the hypothalamic-pituitary-adrenocortical system in mothers and newborns in the Democratic Republic of Congo. Child Dev.87(1), 61–72 (2016).
  • Lei L , Caode Rooij SR , KingSet al. Prenatal stress and epigenetics. Neurosci. Biobehav. Rev.117, 198–210 (2020).
  • Yehuda R , DaskalakisNP , BiererLMet al. Holocaust exposure induced intergenerational effects on FKBP5 methylation. Biol. Psychiatry80(5), 372–380 (2016).
  • Bierer LM , BaderHN , DaskalakisNPet al. Intergenerational effects of maternal holocaust exposure on FKBP5 methylation. Am. J. Psychiatry177(8), 744–753 (2020).
  • Conrad D , WilkerS , SchneiderAet al. Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma: results from two independent African cohorts. Psychophysiology57(1), e13288 (2020).
  • Munyandamutsa N , NkubamugishaPM , FabryMGet al. Mental and physical health in Rwanda 14 years after the genocide. Soc. Psychiatry Psychiatr. Epidemiol.47(11), 1753–1761 (2012).
  • Schaal S , DusingizemunguJP , JacobNet al. Rates of trauma spectrum disorders and risks of posttraumatic stress disorder in a sample of orphaned and widowed genocide survivors. Eur. J. Psychotraumatol.2 (2011).
  • Perroud N , RutembesaE , GiacobinoAPet al. The Tutsi genocide and transgenerational transmission of maternal stress: epigenetics and biology of the HPA axis. World J. Biol. Psychiatry15(4), 334–345 (2014).
  • Rieder H , ElbertT. Rwanda – lasting imprints of a genocide: trauma, mental health and psychosocial conditions in survivors, former prisoners and their children. Confl. Health7(1), 6 (2013).
  • Vukojevic V , KolassaIT , FastenrathMet al. Epigenetic modification of the glucocorticoid receptor gene is linked to traumatic memory and post-traumatic stress disorder risk in genocide survivors. J. Neurosci.34(31), 10274–10284 (2014).
  • Aryee MJ , JaffeAE , Corrada-BravoHet al. Minfi: a flexible and comprehensive bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics30(10), 1363–1369 (2014).
  • Wani AH , AielloAE , KimGSet al. The impact of psychopathology, social adversity and stress-relevant DNA methylation on prospective risk for post-traumatic stress: a machine learning approach. J. Affect. Disord.282, 894–905 (2013).
  • Leek JT , JohnsonWE , ParkerHSet al. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics (Oxford, England)28(6), 882–883 (2012).
  • Johnson WE , LiC , RabinovicAet al. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics8(1), 118–127 (2006).
  • McCutchan PK , FreedMC , LowECet al. Rescaling the post-traumatic stress disorder checklist for use in primary care. Military Med.181(9), 1002–1006 (2016).
  • Cook TL , ShannonPJ , VinsonGAet al. War trauma and torture experiences reported during public health screening of newly resettled Karen refugees: a qualitative study. BMC Int. Health Human Rights15(1), 8 (2015).
  • Salas LA , KoestlerDC , ButlerRAet al. An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray. Genome Biol.19(1), 64–64 (2018).
  • Teschendorff AE , BreezeCE , ZhengSCet al. A comparison of reference-based algorithms for correcting cell-type heterogeneity in epigenome-wide association studies. BMC Bioinformatics18(1), 105 (2017).
  • Martorell-Marugán J , González-RumayorV , Carmona-SáezPet al. mCSEA: detecting subtle differentially methylated regions. Bioinformatics35(18), 3257–3262 (2019).
  • Ritchie ME , PhipsonB , WuDiet al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res.43(7), e47 (2015).
  • Sergushichev AA . An algorithm for fast preranked gene set enrichment analysis using cumulative statistic calculation. bioRxive060012 (2016).
  • Friedman JH . Greedy function approximation: a gradient boosting machine. Ann. Statist.29(5), 1189–1232 (2001).
  • Etzel L , HastingsWJ , MatternBCet al. Intergenerational transmission of childhood trauma? Testing cellular aging in mothers exposed to sexual abuse and their children. Psychoneuroendocrinology120, 104781 (2020).
  • Herawati N , NisaK , NusyirwanSet al. Regularized multiple regression methods to deal with severe multicollinearity. Int. J. Stati. Appl.8, 167–172 (2018).
  • Sill M , HielscherT , BeckerNet al. c060: Extended inference with lasso and elastic-net regularized Cox and generalized linear models. J. Stat. Software62(5), 2 (2014).
  • Meinshausen N , BühlmannP. Stability selection. J. Royal Stat. Soc.72(4), 417–473 (2010).
  • Braun PR , HanS , HingBet al. Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals. Transl. Psychiatry9(1), 47–47 (2019).
  • Horvath S . DNA methylation age of human tissues and cell types. Genome Biol.14(10), 3156 (2013).
  • Perroud N , RutembesaE , Paoloni-Giacobinoet al. The Tutsi genocide and transgenerational transmission of maternal stress: epigenetics and biology of the HPA axis. World J. Biol. Psychiatry15(4), 334–345 (2014).
  • Mutuyimana C , SeziberaV , NsabimanaEet al. PTSD prevalence among resident mothers and their offspring in Rwanda 25 years after the 1994 genocide against the Tutsi. BMC Psychol.7(1), 84 (2019).
  • Kabakambira JD , UweraG , HategekaMet al. Burden of post-traumatic stress disorder acute exacerbations during the commemorations of the genocide against Tutsis in Rwanda: a cross-sectional study. Pan. Afr. Med. J.30, 216 (2018).
  • Viuff AC , SharpGC , RaidDet al. Maternal depression during pregnancy and cord blood DNA methylation: findings from the Avon Longitudinal Study of Parents and Children. Transl. Psychiatry8(1), 244–244 (2018).
  • Stein A , PearsonRM , GoodmanSHet al. Effects of perinatal mental disorders on the fetus and child. Lancet384(9956), 1800–1819 (2014).
  • Rai D , LeeBK , DalmanCet al. Antidepressants during pregnancy and autism in offspring: population based cohort study. BMJ358, j2811 (2017).
  • Rutten BPF , VermettenE , VinkersCHet al. Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder. Mol. Psychiatry23(5), 1145–1156 (2018).
  • Krzyzewska IM , EnsinkJBM , NawijnLet al. Genetic variant in CACNA1C is associated with PTSD in traumatized police officers. Eur. J. Hum. Genet.26(2), 247–257 (2018).
  • Wamstad JA , CorcoranCM , KeatingAMet al. Role of the transcriptional corepressor Bcor in embryonic stem cell differentiation and early embryonic development. PLoS ONE3(7), e2814–e2814 (2008).
  • Grossmann V , TiacciE , HolmesABet al. Whole-exome sequencing identifies somatic mutations of BCOR in acute myeloid leukemia with normal karyotype. Blood118(23), 6153–6163 (2011).
  • Hilton E , JohnstonJ , WhalenSet al. BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects. Eur. J. Hum. Genet.17(10), 1325–1335 (2009).
  • Davies HR , HodgsonK , SchwalbeEet al. Epigenetic modifiers DNMT3A and BCOR are recurrently mutated in CYLD cutaneous syndrome. Nat. Comm.10(1), 4717–4717 (2019).
  • Evans SJ , ChoudaryPV , NealCRet al. Dysregulation of the fibroblast growth factor system in major depression. Proc. Natl Acad. Sci. USA101(43), 15506–15511 (2004).
  • Deng Z , DengS , ZhangMu Ret al. Fibroblast growth factors in depression. Front. Pharmacol.10, 60–60 (2019).
  • Wang T , ZengZ , HuZet al. FGFR2 is associated with bipolar disorder: a large-scale case-control study of three psychiatric disorders in the Chinese Han population. World J. Biol. Psychiatry13(8), 599–604 (2012).
  • Van Scheltinga AFT , BakkerSC , KahnRS. Fibroblast growth factors in schizophrenia. Schizophr. Bull.36(6), 1157–1166 (2009).
  • Logue MW , MillerWM , WolfEJet al. An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci. Clin. Epigenet.12(1), 46–46 (2020).
  • Walker RM, Christoforou AN, McCartney DL et al. DNA methylation in a Scottish family multiply affected by bipolar disorder and major depressive disorder. Clinical Epigenetics8(1), 5 (2016).
  • Ensink JBM , KedingTJ , HennemanPet al. Differential DNA methylation is associated with hippocampal abnormalities in pediatric posttraumatic stress disorder. Biol. Psychiatry Cogn. Neurosci. Neuroimaging doi:10.1016/j.bpsc.2021.04.016 (2021) ( Epub ahead of print).
  • Mehta D , PelzerES , BrueningDet al. DNA methylation from germline cells in veterans with PTSD. J. Psychiatr. Res.116, 42–50 (2019).
  • Wray NR , RipkeS , MattheisenMet al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat. Genet.50(5), 668–681 (2018).
  • Komai T , IwarariH , MochizukiYet al. Expression of the mouse PR domain protein Prdm8 in the developing central nervous system. Gene Expr. Patterns9(7), 503–514 (2009).
  • Joubert BR , JanineF Felix , YousefiPet al. DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis. Am. J. Human Genet.98(4), 680–696 (2016).
  • Khan MHR , BhadraA , HowladerTet al. Stability selection for lasso, ridge and elastic net implemented with AFT models. Stat. Appl. Genet. Mol. Biol.18(5), 2019).
  • Joo JE , NovakovicB , CruickshankMet al. Human active X-specific DNA methylation events showing stability across time and tissues. Eur. J. Human Genet.22(12), 1376–1381 (2014).
  • Jaffe AE , GaoY , Deep-SoboslayAet al. Mapping DNA methylation across development, genotype and schizophrenia in the human frontal cortex. Nat. Neurosci.19(1), 40–47 (2016).
  • Abdolmaleky HM , YaqubiS , PapageorgisPet al. Epigenetic dysregulation of HTR2A in the brain of patients with schizophrenia and bipolar disorder. Schizophr. Res.129(2-3), 183–190 (2011).
  • Sabunciyan S , AryeeMJ , IrizarryRAet al. Genome-wide DNA methylation scan in major depressive disorder. PLoS ONE7(4), e34451 (2012).

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