Evidence of Inbreeding in Hodgkin Lymphoma

PLoS One. 2016 Apr 28;11(4):e0154259. doi: 10.1371/journal.pone.0154259. eCollection 2016.

Abstract

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.

MeSH terms

  • Alleles
  • Case-Control Studies
  • Consanguinity*
  • Female
  • Gene Frequency
  • Genes, Recessive
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome, Human
  • Genome-Wide Association Study
  • Germany
  • Hodgkin Disease / diagnosis
  • Hodgkin Disease / genetics*
  • Hodgkin Disease / pathology
  • Homozygote*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Reproduction / genetics*
  • Selection, Genetic*

Grants and funding

The authors have no support or funding to report.