title: Heritability of liver enzyme levels estimated from genome-wide SNP data.
abstract: Variation in the liver enzyme levels in humans is moderately heritable, as indicated by twin-family studies. At present, genome-wide association studies have traced <2% of the variance back to genome-wide significant single-nucleotide polymorphisms (SNPs). We estimated the SNP-based heritability of levels of three liver enzymes (gamma-glutamyl transferase (GGT); alanine aminotransferase (ALT); and aspartate aminotransferase (AST)) using genome-wide SNP data in a sample of 5421 unrelated Dutch individuals. Two estimation methods for SNP-based heritability were compared, one based on the distant genetic relatedness among all subjects as summarized in a Genetic Relatedness Matrix (GRM), and the other one based on density estimation (DE). The DE method was also applied to meta-analysis results on GGT and ALT. GRM-derived SNP-based heritability estimates were significant for GGT (16%) and AST (11%), but not for ALT (6%). DE estimates in the same sample varied as a function of pruning and were around 23% for all liver enzymes. Application of the DE approach to meta-analysis results for GGT and ALT gave SNP-based heritability estimates of 6 and 3%. The significant results in the Dutch sample indicate that genome-wide SNP platforms contain substantial information regarding the underlying genetic variation in the liver enzyme levels. A major part of this genetic variation remains however undetected. SNP-based heritability estimates, based on meta-analysis results, may point at substantial heterogeneity among cohorts contributing to the meta-analysis. This type of analysis may provide useful information to guide future gene searches.
authors.affiliation: 1] VU University Amsterdam, Department of Biological Psychology, Amsterdam, The Netherlands [2] VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands.
authors.forename: Jenny H D A
authors.initials: JH
authors.lastname: van Beek
authors.affiliation: 1] VU University Amsterdam, Department of Biological Psychology, Amsterdam, The Netherlands [2] University of Notre Dame, Department of Psychology, Notre Dame, IN, USA.
authors.forename: Gitta H
authors.initials: GH
authors.lastname: Lubke
authors.affiliation: 1] VU University Amsterdam, Department of Biological Psychology, Amsterdam, The Netherlands [2] VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands.
authors.forename: Marleen H M
authors.initials: MH
authors.lastname: de Moor
authors.affiliation: 1] VU University Amsterdam, Department of Biological Psychology, Amsterdam, The Netherlands [2] VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands.
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.affiliation: 1] VU University Amsterdam, Department of Biological Psychology, Amsterdam, The Netherlands [2] VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands [3] Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
authors.affiliation: 1] VU University Amsterdam, Department of Biological Psychology, Amsterdam, The Netherlands [2] VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands [3] Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jouke Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.affiliation: University of Notre Dame, Department of Psychology, Notre Dame, IN, USA.
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Walters
authors.affiliation: VU University Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Smit
authors.affiliation: VU University Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: 1] VU University Amsterdam, Department of Biological Psychology, Amsterdam, The Netherlands [2] VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands [3] Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000235:genetics* / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D040582:Inheritance Patterns; D008099:Liver / Q000737:chemistry / Q000201:enzymology*; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D005723:gamma-Glutamyltransferase / Q000235:genetics* / Q000378:metabolism
chemical_list: D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase