title: Heritability estimates on Hodgkin's lymphoma: a genomic- versus population-based approach.
abstract: Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) influencing the risk of Hodgkin's lymphoma (HL) and demonstrated the association of common genetic variation for this type of cancer. Such evidence for inherited genetic risk is also provided by the family history and the very high concordance between monozygotic twins. However, little is known about the genetic and environmental contributions. A common measure for describing the phenotypic variation due to genetics is the heritability. Using GWAS data on 906 HL cases by considering all typed SNPs simultaneously, we have calculated that the common variance explained by SNPs accounts for >35% of the total variation on the liability scale in HL (95% confidence interval 6-62%). These findings are consistent with similar heritability estimates of ∼ 0.40 (95% confidence interval 0.17-0.58) based on Swedish population data. Our estimates support the underlying polygenic basis for susceptibility to HL, and show that heritability based on the population data is somehow larger than heritability based on the genomic data because of the possibility of some missing heritability in the GWAS data. Besides that there is still major evidence for multiple loci causing HL on chromosomes other than chromosome 6 that need to be detected. Because of limited findings in prior GWASs, it seems worth checking for more loci causing susceptibility to HL.
authors.affiliation: German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology, Heidelberg, Germany.
authors.forename: Hauke
authors.initials: H
authors.lastname: Thomsen
authors.affiliation: German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology, Heidelberg, Germany.
authors.forename: Miguel Inacio
authors.initials: MI
authors.lastname: da Silva Filho
authors.affiliation: 1] German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology, Heidelberg, Germany [2] Center for Primary Health Care Research, Lund University, Malmö, Sweden.
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
authors.affiliation: Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Fuchs
authors.affiliation: Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ponader
authors.affiliation: Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany.
authors.forename: Elke Pogge
authors.initials: EP
authors.lastname: von Strandmann
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Lewin
authors.initials: L
authors.lastname: Eisele
authors.affiliation: 1] Institute of Human Genetics and Department of Genomics, University of Bonn, Bonn, Germany [2] Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Herms
authors.affiliation: 1] Institute of Human Genetics and Department of Genomics, University of Bonn, Bonn, Germany [2] Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Per
authors.initials: P
authors.lastname: Hofmann
authors.affiliation: Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Sundquist
authors.affiliation: Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
authors.affiliation: 1] German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology, Heidelberg, Germany [2] Center for Primary Health Care Research, Lund University, Malmö, Sweden.
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006689:Hodgkin Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013548:Sweden