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Advanced paternal age is a risk factor for BPD in the offspring. The results are consistent with the hypothesis that advancing paternal age increases the risk for de novo mutations in susceptibility genes for neurodevelopmental disorders.

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The association between obsessive-compulsive disorder (OCD) and Tourette's/chronic tic disorders (TD/CTD) with autoimmune diseases (ADs) is uncertain. In this nationwide study, we sought to clarify the patterns of comorbidity and familial clustering of a broad range of ADs in individuals with OCD, individuals with TD/CTD and their biological relatives. From a birth cohort of 7 465 455 individuals born in Sweden between 1940 and 2007, we identified 30 082 OCD and 7279 TD/CTD cases in the National Patient Register and followed them up to 31 December 2013. The risk of 40 ADs was evaluated in individuals with OCD, individuals with TD/CTD and their first- (siblings, mothers, fathers), second- (half siblings) and third-degree (cousins) relatives, compared with population controls. Individuals with OCD and TD/CTD had increased comorbidity with any AD (43% and 36%, respectively) and many individual ADs. The risk of any AD and several individual ADs was consistently higher among first-degree relatives than among second- and third-degree relatives of OCD and TD/CTD probands. The risk of ADs was very similar in mothers, fathers and siblings of OCD probands, whereas it tended to be higher in mothers and fathers of TD/CTD probands (compared with siblings). The results suggest a familial link between ADs in general (that is, not limited to Streptococcus-related conditions) and both OCD and TD/CTD. Additional mother-specific factors, such as the placental transmission of antibodies, cannot be fully ruled out, particularly in TD/CTD.

This study provides a reasonable estimation of the incidence of GW in the Swedish population by use of register data, with results comparable to those from previous smaller studies. There was a downward trend of GW incidence among younger females between 2006 and 2010.

Background Advanced paternal age has been linked with neurodevelopmental disorders such as schizophrenia. If age-related de novo mutations in the male germ line underlie this association, it would be expected that grandpaternal as well as paternal age may influence the risk of schizophrenia. The aim of the current study was to explore the links between both paternal and grandpaternal age with respect to the risk of schizophrenia in a large, national register-based sample. Method The study was based on Swedish Multi-Generation and Hospital Discharge Registers. Parents’ ages at offspring birth were compared between 20,582 affected and 100,176 non-affected individuals. Grandparents’ ages at the birth of the parent were compared between 2,511 affected and 15,619 non-affected individuals. The risk of schizophrenia was examined when the predictor variable (parent or grandparent age) was examined in age strata with logistic regression. Planned sensitivity analyses included exploring the variables of interest in males and females separately. Results After adjusting for maternal age, birth year and sex of the proband, we confirmed that the offspring of older fathers have an increased risk of schizophrenia (e.g. compared to paternal age 20–24 years, those with fathers > 55 years had a two-fold increased risk). With respect to grandparent age, older maternal (but not paternal) grandfather age was associated with an increased risk of schizophrenia. Compared to maternal grandfather age 20–24 years, those with maternal grandfathers >55 years had a significantly increased risk of schizohrpenia (Adjusted Odds ratio and 95% Confidence intervals; 2.79, 1.71 – 4.56). The pattern of findings were essentially unchanged when we examine male and female probands separately. Conclusion This is the first the study to show an association between grandpaternal age and risk of schizophrenia. The selective effect of advanced maternal grandfather age suggests that the biological mechanisms involving the X chromosome may differentially contribute to the association between paternal age and risk of schizophrenia.

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Higher paternal age at offspring conception increases de novo genetic mutations. Based on evolutionary genetic theory we predicted older fathers' children, all else equal, would be less likely to survive and reproduce, i.e. have lower fitness. In sibling control studies, we find support for negative paternal age effects on offspring survival and reproductive success across four large populations with an aggregate N > 1.4 million. Three populations were pre-industrial (1670–1850) Western populations and showed negative paternal age effects on infant survival and offspring reproductive success. In twentieth-century Sweden, we found minuscule paternal age effects on survival, but found negative effects on reproductive success. Effects survived tests for key competing explanations, including maternal age and parental loss, but effects varied widely over different plausible model specifications and some competing explanations such as diminishing paternal investment and epigenetic mutations could not be tested. We can use our findings to aid in predicting the effect increasingly older parents in today's society will have on their children's survival and reproductive success. To the extent that we succeeded in isolating a mutation-driven effect of paternal age, our results can be understood to show that de novo mutations reduce offspring fitness across populations and time periods.