Evidence of Inbreeding in Hodgkin Lymphoma.
Genome-wide association studies (GWASs) have identified several, mainly co-dominantly acting, single-nucleotide polymorphisms (SNPs) associated with Hodgkin lymphoma (HL). We searched for recessively acting disease loci by performing an analysis of runs of homozygosity (ROH) based on windows of homozygous SNP-blocks and by calculating genomic inbreeding coefficients on a SNP-wise basis. We used data from a previous GWAS with 906 cases and 1217 controls from a population with a long history of no matings between relatives. Ten recurrent ROHs were identified among 25 055 ROHs across all individuals but their association with HL was not genome-wide significant. All recurrent ROHs showed significant evidence for natural selection. As a novel finding genomic inbreeding among cases was significantly higher than among controls (P = 2.11*10-14) even after correcting for covariates. Higher inbreeding among the cases was mainly based on a group of individuals with a higher average length of ROHs per person. This result suggests a correlation of higher levels of inbreeding with higher cancer incidence and might reflect the existence of recessive alleles causing HL. Genomic inbreeding may result in a higher expression of deleterious recessive genes within a population.
German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology (C050), Heidelberg, 69120, Germany.
Hauke
H
Thomsen
German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology (C050), Heidelberg, 69120, Germany.
Miguel
M
Inacio da Silva Filho
Department of Internal Medicine I, University Hospital of Cologne, Cologne, 50924, Germany.
Michael
M
Fuchs
Department of Internal Medicine I, University Hospital of Cologne, Cologne, 50924, Germany.
Sabine
S
Ponader
Department of Internal Medicine I, University Hospital of Cologne, Cologne, 50924, Germany.
Elke
E
Pogge von Strandmann
Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University Duisburg-Essen, Essen, 45122, Germany.
Lewin
L
Eisele
Institute of Human Genetics and Department of Genomics, University of Bonn, Bonn, 53127, Germany.|Department of Biomedicine, Division of Medical Genetics, Basel, University of Basel, 4058, Switzerland.
Stefan
S
Herms
Institute of Human Genetics and Department of Genomics, University of Bonn, Bonn, 53127, Germany.|Department of Biomedicine, Division of Medical Genetics, Basel, University of Basel, 4058, Switzerland.
Per
P
Hoffmann
Department of Internal Medicine I, University Hospital of Cologne, Cologne, 50924, Germany.
Andreas
A
Engert
German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology (C050), Heidelberg, 69120, Germany.|Center for Primary Health Care Research, Lund University, Malmö, 20502, Sweden.
Kari
K
Hemminki
German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology (C050), Heidelberg, 69120, Germany.|Center for Primary Health Care Research, Lund University, Malmö, 20502, Sweden.
Asta
A
Försti
D000483:Alleles; D016022:Case-Control Studies; D003241:Consanguinity; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005858:Germany; D006689:Hodgkin Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012098:Reproduction / Q000235:genetics*; D012641:Selection, Genetic