Do autism-related personality traits explain higher paternal age in autism?

Abstract

brium (LD) and located in the 3 0 region of the second LD block within the ACE gene, identified as described in Baghai and co-workers, which spans the promoter region as well as all coding regions for ACE isoforms 1 and 2. 2,7 Only for rs4311, the P-value was still significant after Bonferroni correction for multiple testing (Table 1). All five SNPs entered the replication and significant P-values after Bonferroni correction were found for rs4311 and rs4333 (Table 1); rs4329 (P = 0.04), rs4344 (P = 0.01), rs4353 (P = 0.04) were nominally associated in sample 2.Although the association replicated in both samples, the direction of this association was different. The T allele of rs4311 and 4333 was the risk allele in sample 1, while we observed a heterozygous disadvantage for both SNPs in sample 2. The reason for true but diverse, in extreme reversed associations, known as the flip-flop phenomenon, are discussed in a recent publication by Lin et al. 8 Flip-flop associations may indicate heterogeneous effects of the same true variant due to differences in the LD structure between the genotyped SNPs and the disease susceptibility locus in two investigated samples. 8 Following this idea, the reported SNPs could be non-causal but in LD with a genuine causal variant and/or multilocus effects that we are not able to account for, and this may lead to different associations. Interestingly, these SNPs are located in the same LD block as the promoter variant associated with unipolar depression, but are clustered at the 3 0 end of this block. While the variant rs4291 associated with unipolar depression was not significantly associated with panic disorders, all of the five SNPs associated with panic disorder were also nominally associated with unipolar depression. 2 The ACE gene may thus be an example for a genetic or locus overlap between anxiety and depression.Taken together, we have identified an association of two SNPs (rs4311 and rs4333) in the ACE gene with syndromal panic attacks, which could be replicated in an independent case/control sample, although in a different direction. Further studies have to be performed to elucidate the functional correlates of this association, especially regarding ACE activity in vivo in patients with panic attacks.

Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies

“…Such traits (e.g., shyness) could manifest as reduced ability for social interaction and may result in an older paternal age (14). Our familybased analysis examined this hypothesis by comparing paternal age in siblings with and without autism.…”

“…These include high levels of missing-data, selection bias, and lack of statistical control for other risk factors (e.g., age of the other parent, birth order, perinatal complications, or presence of psychiatric disorders in parents). It has also been suggested that the association is due to fathers of autistic individuals delaying paternity because they carry traits associated with the autism phenotype (14). For example, traits such as shyness and aloofness which may limit interactions with women have been described in fathers of autistic children (15,16).…”

Environmental factors associated with autism spectrum disorder: a scoping review for the years 2003–2013

“…120,121 No association has been found between men with autistic-like traits and delayed parenting. 122,123 A 2012 meta-analysis found the relative risk (RR) of ASD for mothers aged 35 years or over compared to those aged 25 to 29 years to be 1.31 (95% CI: 1.19-1.45). 114 Since the most recent systematic review, 114 four studies have found significant associations between advanced maternal age and ASD 117,118,124,125 and one did not.…”

Facteurs environnementaux associés au trouble du spectre de l’autisme : étude de délimitation portant sur les années 2003 à 2013

“…Des mutations de novo et des variations du nombre de copies du génome ont été mises en cause comme mécanisme sous-jacent possible, parce qu'elles augmentent en fonction de l'âge des parents 120,121 . On n'a trouvé aucun lien entre les hommes présentant des caractéris-tiques semblables à l'autisme et le fait de devenir parent plus tard 122,123 .…”