title: Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children.
abstract: BACKGROUND
  Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposity in later life. Epigenetic modification is suggested as a plausible mediating mechanism.
  
  
  METHODS
  We used multivariable linear regression and a negative control design to examine offspring epigenome-wide DNA methylation in relation to maternal and offspring adiposity in 1018 participants.
  
  
  RESULTS
  Compared with neonatal offspring of normal weight mothers, 28 and 1621 CpG sites were differentially methylated in offspring of obese and underweight mothers, respectively [false discovert rate (FDR)-corrected P-value < 0.05), with no overlap in the sites that maternal obesity and underweight relate to. A positive association, where higher methylation is associated with a body mass index (BMI) outside the normal range, was seen at 78.6% of the sites associated with obesity and 87.9% of the sites associated with underweight. Associations of maternal obesity with offspring methylation were stronger than associations of paternal obesity, supporting an intrauterine mechanism. There were no consistent associations of gestational weight gain with offspring DNA methylation. In general, sites that were hypermethylated in association with maternal obesity or hypomethylated in association with maternal underweight tended to be positively associated with offspring adiposity, and sites hypomethylated in association with maternal obesity or hypermethylated in association with maternal underweight tended to be inversely associated with offspring adiposity.
  
  
  CONCLUSIONS
  Our data suggest that both maternal obesity and, to a larger degree, underweight affect the neonatal epigenome via an intrauterine mechanism, but weight gain during pregnancy has little effect. We found some evidence that associations of maternal underweight with lower offspring adiposity and maternal obesity with greater offspring adiposity may be mediated via increased DNA methylation.
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and gemma.sharp@bristol.ac.uk.
authors: Gemma C
authors: GC
authors: Sharp
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and.
authors: Debbie A
authors: DA
authors: Lawlor
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and.
authors: Rebecca C
authors: RC
authors: Richmond
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and.
authors: Abigail
authors: A
authors: Fraser
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and.
authors: Andrew
authors: A
authors: Simpkin
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and.
authors: Matthew
authors: M
authors: Suderman
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and.
authors: Hashem A
authors: HA
authors: Shihab
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and.
authors: Oliver
authors: O
authors: Lyttleton
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and.
authors: Wendy
authors: W
authors: McArdle
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and.
authors: Susan M
authors: SM
authors: Ring
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and.
authors: Tom R
authors: TR
authors: Gaunt
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and.
authors: George
authors: G
authors: Davey Smith
authors: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK and Institute of Genetic Medicine, University of Newcastle, Newcastle upon Tyne, UK.
authors: Caroline L
authors: CL
authors: Relton
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000293:Adolescent; D015992:Body Mass Index; D002648:Child; D019175:DNA Methylation; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009765:Obesity / Q000235:genetics*; D044343:Overnutrition; D011247:Pregnancy; D013851:Thinness; D006113:United Kingdom; D015430:Weight Gain
keywords: ALSPAC; ARIES; Epigenetic; causality; epigenome-wide association study; longitudinal; overnutrition; overweight; undernutrition