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No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study


It is well known that mating between relatives increases the risk that a child will have a rare recessive genetic disease, but there has also been increasing interest and inconsistent findings on whether inbreeding is a risk factor for common, complex psychiatric disorders such as schizophrenia. The best powered study to date investigating this theory predicted that the odds of developing schizophrenia increase by approximately 17% for every additional percent of the genome that shows evidence of inbreeding. In this replication, we used genome-wide single nucleotide polymorphism data from 18,562 schizophrenia cases and 21,268 controls to quantify the degree to which they were inbred and to test the hypothesis that schizophrenia cases show higher mean levels of inbreeding. Contrary to the original study, we did not find evidence for distant inbreeding to play a role in schizophrenia risk. There are various confounding factors that could explain the discrepancy in results from the original study and our replication, and this should serve as a cautionary note–careful attention should be paid to issues like ascertainment when using the data from genome-wide case-control association studies for secondary analyses for which the data may not have originally been intended.


Vyšlo v časopise: No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study. PLoS Genet 12(10): e32767. doi:10.1371/journal.pgen.1006343
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1006343

Souhrn

It is well known that mating between relatives increases the risk that a child will have a rare recessive genetic disease, but there has also been increasing interest and inconsistent findings on whether inbreeding is a risk factor for common, complex psychiatric disorders such as schizophrenia. The best powered study to date investigating this theory predicted that the odds of developing schizophrenia increase by approximately 17% for every additional percent of the genome that shows evidence of inbreeding. In this replication, we used genome-wide single nucleotide polymorphism data from 18,562 schizophrenia cases and 21,268 controls to quantify the degree to which they were inbred and to test the hypothesis that schizophrenia cases show higher mean levels of inbreeding. Contrary to the original study, we did not find evidence for distant inbreeding to play a role in schizophrenia risk. There are various confounding factors that could explain the discrepancy in results from the original study and our replication, and this should serve as a cautionary note–careful attention should be paid to issues like ascertainment when using the data from genome-wide case-control association studies for secondary analyses for which the data may not have originally been intended.


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