Evidence of Inbreeding in Hodgkin Lymphoma

• Published in: PloS one 2016-04, Vol.11 (4), p.e0154259-e0154259
• Main Authors: Thomsen, Hauke, Inacio da Silva Filho, Miguel, Fuchs, Michael, Ponader, Sabine, Pogge von Strandmann, Elke, Eisele, Lewin, Herms, Stefan, Hoffmann, Per, Engert, Andreas, Hemminki, Kari, Försti, Asta
• Format: Article
• Language: English
• Subjects: Alleles; Analysis; Basic Medicine; Biology and Life Sciences; Cancer; Case-Control Studies; Consanguinity; Disease; Epidemiology; Female; Gene expression; Gene Frequency; Generalized linear models; Genes, Recessive; Genetic Loci; Genetic Predisposition to Disease; Genetics; Genome, Human; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Germany; Hodgkin Disease - diagnosis; Hodgkin Disease - genetics; Hodgkin Disease - pathology; Hodgkin's disease; Hodgkin's lymphoma; Homozygosity; Homozygote; Hospitals; Humans; Inbreeding; Internal medicine; Lymphoma; Male; Medical and Health Sciences; Medical Genetics; Medical research; Medicin och hälsovetenskap; Medicine; Medicine and Health Sciences; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Mens health; Natural selection; Physical Sciences; Polymorphism, Single Nucleotide; Primary care; Reproduction - genetics; Risk factors; Selection, Genetic; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Studies; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0154259

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.