title: The association of alcohol intake with γ-glutamyl transferase (GGT) levels: evidence for correlated genetic effects.
abstract: BACKGROUND
  Blood levels of gamma-glutamyl transferase (GGT) are used as a marker for (heavy) alcohol use. The role of GGT in the anti-oxidant defense mechanism that is part of normal metabolism supposes a causal effect of alcohol intake on GGT. However, there is variability in the response of GGT to alcohol use, which may result from genetic differences between individuals. This study aimed to determine whether the epidemiological association between alcohol intake and GGT at the population level is necessarily a causal one or may also reflect effects of genetic pleiotropy (genes influencing multiple traits).
  
  
  METHODS
  Data on alcohol intake (grams alcohol/day) and GGT, originating from twins, their siblings and parents (N=6465) were analyzed with structural equation models. Bivariate genetic models tested whether genetic and environmental factors influencing alcohol intake and GGT correlated significantly. Significant genetic and environmental correlations are consistent with a causal model. If only the genetic correlation is significant, this is evidence for genetic pleiotropy.
  
  
  RESULTS
  Phenotypic correlations between alcohol intake and GGT were significant in men (r=.17) and women (r=.09). The genetic factors underlying alcohol intake correlated significantly with those for GGT, whereas the environmental factors were weakly correlated (explaining 4-7% vs. 1-2% of the variance in GGT respectively).
  
  
  CONCLUSIONS
  In this healthy population sample, the epidemiological association of alcohol intake with GGT is at least partly explained by genetic pleiotropy. Future longitudinal twin studies should determine whether a causal mechanism underlying this association might be confined to heavy drinking populations.
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: J.H.D.A.van.Beek@vu.nl.
authors.forename: Jenny H D A
authors.initials: JHDA
authors.lastname: van Beek
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marleen H M
authors.initials: MHM
authors.lastname: de Moor
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lot M
authors.initials: LM
authors.lastname: Geels
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands.
authors.forename: Michel R T
authors.initials: MRT
authors.lastname: Sinke
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eco J C
authors.initials: EJC
authors.lastname: de Geus
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands; University of Notre Dame, Department of Psychology, 118 Haggar Hall, Notre Dame, IN 46556, USA.
authors.forename: Gitta H
authors.initials: GH
authors.lastname: Lubke
authors.affiliation: Good Biomarker Sciences, Zernikedreef 8, 2333 CL Leiden, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Kluft
authors.affiliation: Good Biomarker Sciences, Zernikedreef 8, 2333 CL Leiden, The Netherlands.
authors.forename: Jacoline
authors.initials: J
authors.lastname: Neuteboom
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Vink
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D003625:Data Collection / Q000379:methods; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D012042:Registries; D014427:Twins / Q000235:genetics*; D005723:gamma-Glutamyltransferase / Q000097:blood* / Q000235:genetics*
chemical_list: D015415:Biomarkers; D005723:gamma-Glutamyltransferase
keywords: Alcohol use; Causality; Gamma-glutamyl transferase (GGT); Genetic pleiotropy; Heritability; Liver enzymes