Evidence of Inbreeding in Hodgkin Lymphoma.

Authors:
Hauke Thomsen, Dr.
Hauke Thomsen, Dr.
GeneWerk GmbH
Senior Bioinformatician
Bioinformatics, Biostatistics, Genetics
Heidelberg, Baden-Württemberg/Germany | Germany
Michael Fuchs
Michael Fuchs
University Hospital of Cologne
Germany
Sabine Ponader
Sabine Ponader
University of Erlangen-Nuremberg
Germany
Lewin Eisele
Lewin Eisele
Institute for Medical Informatics
Germany
Stefan Herms
Stefan Herms
Institute of Human Genetics
Germany
Per Hoffmann
Per Hoffmann
Institute of Human Genetics
Germany

PLoS One 2016 28;11(4):e0154259. Epub 2016 Apr 28.

German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology (C050), Heidelberg, 69120, Germany.

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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Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154259PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849743PMC

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