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Evidence of Inbreeding in Hodgkin Lymphoma

Thomsen, Hauke LU ; Inacio da Silva Filho, Miguel; Fuchs, Michael; Ponader, Sabine; Pogge von Strandmann, Elke; Eisele, Lewin; Herms, Stefan; Hoffmann, Per; Engert, Andreas and Hemminki, Kari LU , et al. (2016) In PLoS ONE 11(4).
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... (More)

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.

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4
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  • scopus:85006909761
ISSN
1932-6203
DOI
10.1371/journal.pone.0154259
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English
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30a204a2-b66f-44ce-9dd6-be91373c92be
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@article{30a204a2-b66f-44ce-9dd6-be91373c92be,
  abstract     = {<p>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.</p>},
  articleno    = {e0154259},
  author       = {Thomsen, Hauke and Inacio da Silva Filho, Miguel and Fuchs, Michael and Ponader, Sabine and Pogge von Strandmann, Elke and Eisele, Lewin and Herms, Stefan and Hoffmann, Per and Engert, Andreas and Hemminki, Kari and Försti, Asta},
  issn         = {1932-6203},
  language     = {eng},
  number       = {4},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Evidence of Inbreeding in Hodgkin Lymphoma},
  url          = {http://dx.doi.org/10.1371/journal.pone.0154259},
  volume       = {11},
  year         = {2016},
}