Paternal age as a risk factor for schizophrenia points to epigenetics as being involved in inheritance of schizophrenia

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Paternal age is a risk factor for schizophrenia. There is no evidence of deleterious genetic loci in schizophrenia except for some very rare high impact alleles. Genetic loci associated with schizophrenia are common variants which points to such genetic loci conferring increased fitness leading to such genetic loci being conserved. .

Besides there being no evidence of deleterious genetic loci in schizophrenia except for some very rare high impact alleles.there is not enough time in spermatogenesis to accumulate a lot of mutations. For humans, the entire process of spermatogenesis is variously estimated as taking 74 days[8][9] (according to tritium-labelled biopsies) and approximately 120 days[10] (according to DNA clock measurements).

DNA methylation and histone methylation occurs in spermatogenesis. Dysregulation of epigenetic mechanisms could have occurred over time in aged dads resulting is dysregulation of spermatogenesis. This does not answer the question of how methyl marks are not stripped from embryos, however, the circumstantial evidence points to epigenetic dysregulations rather than genetic mutations as being the factor in paternal age which increases the risk for schizophrenia in offspring.

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