title: Effects of paternal age and offspring cognitive ability in early adulthood on the risk of schizophrenia and related disorders.
abstract: Advanced paternal age (APA) and intelligence quotient (IQ) are both associated with the risk of schizophrenia spectrum disorder (SSD) in young adult offspring. We hypothesized that the offspring SSD risk gradient associated with paternal age is mediated by offspring IQ. We investigated joint and separate associations of paternal age and offspring IQ with the risk of SSD. We used IQ routinely measured at conscription in Danish males (n=138,966) from cohorts born in 1955-84 and in 1976-1993 and followed them from a year after the conscription through 2010. We used Cox regression to estimate the incidence rate ratio (IRR) of SSD. During the follow-up, 528 men developed SSD (incidence rate [IR] 5.2 and 8.6 per 10,000 person-years in the first and second cohorts, respectively). APA was associated with higher risk of SSD (IRR, 1.32; 95% CI, 1.10-1.60 per a ten-year increase in paternal age). A higher IQ was associated with lower SSD risk (IRR, 0.68; 95% confidence interval [CI], 0.63-0.74 per one SD increase). The IR of SSD was higher among persons who were draft-exempt for health reasons (<20% of the men). Overall, there was little evidence of lower premorbid IQ in APA-related SSD (individuals who developed SSD and were also offspring of older fathers). Our results do not support the notion that risk gradient for offspring SSD associated with paternal age is mediated by offspring IQ.
authors.affiliation: Mental Health Centre, Capital Region of Denmark, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark. Electronic address: holger.jelling.soerensen@regionh.dk.
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Sørensen
authors.affiliation: National Centre for Register-Based Research, Aarhus University, Fuglesangs Allé 4, DK-8210 Aarhus V, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
authors.forename: Carsten B
authors.initials: CB
authors.lastname: Pedersen
authors.affiliation: Mental Health Centre, Capital Region of Denmark, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
authors.forename: Merete
authors.initials: M
authors.lastname: Nordentoft
authors.affiliation: National Centre for Register-Based Research, Aarhus University, Fuglesangs Allé 4, DK-8210 Aarhus V, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
authors.forename: Preben B
authors.initials: PB
authors.lastname: Mortensen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark.
authors.forename: Vera
authors.initials: V
authors.lastname: Ehrenstein
authors.affiliation: National Centre for Register-Based Research, Aarhus University, Fuglesangs Allé 4, DK-8210 Aarhus V, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Petersen
mesh_terms: D000328:Adult; D001722:Birth Order; D003071:Cognition; D003718:Denmark / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007360:Intelligence; D007361:Intelligence Tests; D008297:Male; D008875:Middle Aged; D010331:Paternal Age; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000453:epidemiology*; D012306:Risk; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology*; D012569:Schizotypal Personality Disorder / Q000453:epidemiology*; D055815:Young Adult
keywords: General cognitive ability; Intelligence; Paternal age; Schizophrenia; Schizophrenia-spectrum disorder