title: Longitudinal weight differences, gene expression and blood biomarkers in BMI-discordant identical twins.
abstract: BACKGROUND
  Body mass index (BMI) discordant monozygotic (MZ) twins allow an examination of the causes and consequences of adiposity in a genetically controlled design. Few studies have examined longitudinal BMI discordance in MZ pairs.
  
  
  OBJECTIVE
  The aim of this work was to study the development over time of BMI discordance in adolescent and adult MZ twin pairs and to examine lifestyle, metabolic, inflammatory and gene expression differences associated with concurrent and long-term BMI discordance in MZ pairs.
  
  
  METHODS
  BMI data from 2775 MZ twin pairs, collected in eight longitudinal surveys and a biobank project between 1991 and 2011, were analyzed to characterize longitudinal discordance. Lifestyle characteristics were compared within discordant pairs (ΔBMI⩾3 kg m(-2)) and biomarkers (lipids, glucose, insulin, C-reactive protein, fibrinogen, interleukin (IL)-6, tumor necrosis factor-α and soluble IL-6 receptor and liver enzymes aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transferase) and gene expression were compared in peripheral blood from discordant pairs who participated in the Netherlands Twin Register biobank project.
  
  
  RESULTS
  The prevalence of discordance ranged from 3.2% in 1991 (mean age=17, s.d.=2.4) to 17.4% (N=202 pairs) in 2009 (mean age=35, s.d.=15) and was 16.5% (N=174) among pairs participating in the biobank project (mean age=35, s.d.=12). Of the 699 MZ pairs with BMI data from 3 to 5 time points, 17 pairs (2.4%) were long-term discordant (at all available time points; mean follow-up range=6.4 years). Concurrently discordant pairs showed significant differences in self-ratings of which twin eats most (P=2.3 × 10(-13)) but not in leisure time exercise activity (P=0.28) and smoking (P>0.05). Ten out of the 14 biomarkers showed significantly more unfavorable levels in the heavier of twin of the discordant pairs (P-values <0.001); most of these biomarker differences were largest in longitudinally discordant pairs. No significant gene expression differences were identified, although high ranking genes were enriched for Gene Ontology terms highlighting metabolic gene regulation and inflammation pathways.
  
  
  CONCLUSIONS
  BMI discordance is uncommon in adolescent identical pairs but increases with higher pair-mean of BMI at older ages, although long-term BMI discordance is rare. In discordant pairs, the heavier twin had a more unfavorable blood biomarker profile than the genetically matched leaner twin, in support of causal effects of obesity.
authors.affiliation: 1] Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands [2] EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Dongen
authors.affiliation: 1] Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands [2] EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Willemsen
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: B T
authors.initials: BT
authors.lastname: Heijmans
authors.affiliation: Good Biomarker Sciences, Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Neuteboom
authors.affiliation: Good Biomarker Sciences, Leiden, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Kluft
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Jansen
authors.affiliation: 1] EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands [2] Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: B W J
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: P E
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: 1] Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands [2] EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: E J C
authors.initials: EJ
authors.lastname: de Geus
authors.affiliation: 1] Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands [2] EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: D I
authors.initials: DI
authors.lastname: Boomsma
mesh_terms: D050154:Adiposity / Q000235:genetics; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D015444:Exercise; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000097:blood; D008019:Life Style; D008055:Lipids / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D019947:Receptors, Interleukin-6 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014430:Twins, Monozygotic
chemical_list: D015415:Biomarkers; D007328:Insulin; D008055:Lipids; D019947:Receptors, Interleukin-6; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen; D002097:C-Reactive Protein