ASD is an extremely puzzling disorder –– undoubtedly the combination of genetics, epigenetics and environment. I just checked PubMed with the words “autism etiology review” and there are >3,400 REVIEWS alone, on this topic! The term “infantile autism” was first coined in 1908; this term was first listed in Diagnosis and Statistical Manual of Mental Disorders (DSM) in the 1980s. It was only as recently as 2013 that a variety of similar disorders were all combined and named “autism spectrum disorder” [https://www.parents.com/health/autism/the-history-of-autism/].
Without a doubt, ASD represents a multifactorial trait meaning that it is polygenic (contributions from hundreds if not thousands of genes; most genes each having small-effect but some variants could elicit large-effect on the trait), and is affected by epigenetic and environmental factors.
Under the category of genetics –– genome-wide association studies (GWAS; involving thousands of patients and controls in various cohorts and ethnic groups) have uncovered dozens of single-nucleotide variants (SNVs) in or near genes, at least some of which are credible candidates linked to neurodevelopment. Whole-genome sequencing (WGS) studies have found a predominance of copy-number variants (CNVs) on certain chromosomes. Other WGS searches have detected substantial increases in repetitive DNA regions. Other studies have found large DNA deletions in specific chromosomal regions. Nobody knows with any certainty, however, what these WGS investigations mean (with regard to ASD etiology).
Under the category of epigenetics –– significant differences in DNA-methylation patterns and microRNAs have been reported to be associated with increased risk of ASD. There are less convincing studies on histone modifications and chromosome remodeling linked to ASD. Epigenetic factors must be involved in ASD risk, if we consider that sometimes one twin can be afflicted with this disorder, but not the other, within identical twin-pairs.
Under the category of environment, this is where (your question, Fred) “maternal age at the time of conception” must be considered. [And what other factors, besides this, might be associated with “increased affluence,” as mentioned in the article below? What is different in the 1988-2018 era than that in 1930-1960?] “Paternal age at the time of conception” has been implicated. Even recent vaccines and mercury in tooth-fillings have been proposed as a cause. Greatly increased sugar in the diets of babies and young children (and accompanying deficiencies in various vitamins and minerals). Greatly increased amounts of television-viewing, and hours & hours (each & every day) of rapid-eye-movement stimulation via today’s video games and the Hollywood children’s movies and action movies.
I’m sure this list of factors is not complete, but I’ll stop here. You can see ASD is like the “seven blind men perceiving an elephant.” What many epidemiologists and clinical molecular geneticists look for –– is sometimes what they find. 😉
Subject: Re: More children diagnosed with autism spectrum disorder (ASD) in recent years
Dan, has anyone looked at a correlation between women’s age at childbirth with incidence?
I have always suspected this.