Summary: A new study confirms previous findings that males have a higher risk of ASD than females. However, researchers discovered, regardless of gender, siblings born after a female child with autism had an increased risk of ASD than those born after a male on the spectrum.
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling’s gender influences this risk has remained largely unknown.
Now new research led by scientists at Harvard Medical School has for the first time successfully quantified the likelihood that a family who has one child with autism would have another one with the same disorder based on the siblings’ gender.
Overall, the results, published Sept. 25 in JAMA Pediatrics, reveal that having an older female child diagnosed with autism spelled elevated risk for younger siblings and that the risk was highest among younger male siblings. They also affirm past research findings that having one child with autism or an autism spectrum disorder (ASD) portends higher risk for subsequent children, that the disorder is somewhat rare—slightly more than 1.2 percent of children in the study were affected— and that boys have a notably higher overall risk than girls.
The findings can arm physicians and genetic counselors with information useful in counseling families and clarifying the risk for younger siblings in families who already have one child with autism.
“Our results give us a fair degree of confidence to gauge the risk of autism recurrence in families affected by it based on a child’s gender,” said study first author Nathan Palmer, instructor in biomedical informatics at HMS. “It is important to be able to provide worried parents who have one child with the condition some sense of what they can expect with their next child. That information is critical given how much better we’ve become at screening for the disease earlier and earlier in life.”
Such knowledge, the researchers added, could be particularly important in light of physicians’ growing ability to detect autism’s manifestations early in a child’s life and intervene promptly.
“This study is a powerful example of how big data can illuminate patterns and give us insights that allow us to empower parents and pediatricians to implement anticipatory and far more precise medicine,” said study senior author Isaac Kohane, head of the Department of Biomedical Informatics at HMS.
The newly published results stem from the largest study of its kind. Researchers analyzed de-identified health insurance records of more than 1.5 million U.S. families with two children between the ages of 4 and 18, tracking patterns of recurrence among siblings over a year or longer. Of the more than 3.1 million children in the study, some 39,000, or about 1.2 percent—2 percent of boys and 0.5 percent of girls—received a diagnosis of autism or an ASD.
The results confirm previous research showing that, overall, boys have a higher risk of autism and related disorders than girls.
The results, however, also reveal a curious pattern of recurrence based on gender: Siblings born after a female child with autism or a related disorder had a higher risk than siblings born after a male child with autism. Male children were, overall, more susceptible to autism than females. In other words, boys with older female siblings with autism had the highest risk for autism themselves, while female siblings with older brothers with autism had the lowest risk.
For every 100 boys with an older female sibling with autism, 17 received a diagnosis of autism or a related disorder. Male children with older male siblings with ASD had a 13 percent risk of an ASD diagnosis, followed by younger female siblings with older male siblings with ASD (7.6 percent). The lowest risk—4 percent—was observed among younger female siblings who had an older brother with autism or an ASD.
The investigators caution that families should keep the risk in perspective because autism and related disorders remain relatively rare, affecting roughly 1 percent of the general population.
“Even for the group at highest risk—males with an older female sibling with autism—the odds are still about five to one that the child will be unaffected,” Palmer said. “What we have provided here is context for families who already have children with autism or another similar disorder and need a clearer perspective on recurrence risk.”
The results, the researchers said, underscore the notion that autism and related disorders likely arise from the complex interplay between genes and environment and, for reasons yet to be understood, these conditions disproportionately affect more males than females even within families. The stark gender variance, however, hints at a possible role of inherent biological sex differences that may precipitate the development of such disorders under the right environmental conditions, the research team said.
Autism-spectrum disorders are neurodevelopmental conditions that typically emerge in the first few years. They are marked by a range of brain problems, impaired social interactions and compromised communication skills. The Centers for Disease Control and Prevention estimate that autism spectrum disorders affect 1 in 68 children in the United States, with males having four times greater risk than females—an observation also borne out in the new study.
Yet exactly what portion of these diagnoses are strictly rooted in genetic mutation and how many are influenced by environmental factors has long mystified scientists. While some forms of autism arise from a single genetic mutation, most cases appear to be the result of a complex interplay between genes and environment.
Other investigators involved in the study included Andrew Beam, Denis Agniel, Alal Eran, and Arjun Manrai, of Harvard Medical School; Kenneth Mandl of Boston Children’s Hospital; Stanley Nelson of the University of California-Los Angeles; Claire Spettell and Kathe Fox of Aetna, Inc.; and Gregory Steinberg.
Funding: The work was supported in part by Aetna Life Insurance Company.
Source: Ekaterina Pesheva – Harvard
Image Source: NeuroscienceNews.com image is adapted from the Harvard news release.
Original Research: Abstract for “Association of Sex With Recurrence of Autism Spectrum Disorder Among Siblings” by Nathan Palmer, PhD; Andrew Beam, PhD; Denis Agniel, PhD; Alal Eran, PhD; Arjun Manrai, PhD; Claire Spettell, PhD; Gregory Steinberg, MD; Kenneth Mandl, MD; Kathe Fox, PhD; Stanley F. Nelson, MD; and Isaac Kohane, MD, PhD in JAMA Pediatrics. Published online September 25 2017 doi:10.1001/jamapediatrics.2017.2832
Association of Sex With Recurrence of Autism Spectrum Disorder Among Siblings
Importance Autism spectrum disorder (ASD) is known to be more prevalent among males than females in the general population. Although overall risk of recurrence of ASD among siblings has been estimated to be between 6.1% and 24.7%, information on sex-specific recurrence patterns is lacking.
Objective To estimate high-confidence sex-specific recurrence rates of ASD among siblings.
Design, Setting, and Participants This observational study used an administrative database to measure the incidence of ASD among children in 1 583 271 families (37 507 with at least 1 diagnosis of ASD) enrolled in commercial health care insurance plans at a large US managed health care company from January 1, 2008, through February 29, 2016. Families in the study had 2 children who were observed for at least 12 months between 4 and 18 years of age.
Main Outcomes and Measures The primary measure of ASD recurrence was defined as the diagnosis of ASD in a younger sibling of an older sibling with an ASD diagnosis.
Results Among the 3 166 542 children (1 547 266 females and 1 619 174 males; mean [SD] age, 11.2 [4.7] years) in the study, the prevalence of ASD was 1.96% (95% CI, 1.94%-1.98%) among males and 0.50% (95% CI, 0.49%-0.51%) among females. When a male was associated with risk in the family, ASD was diagnosed in 4.2% (95% CI, 3.8%-4.7%) of female siblings and 12.9% (95% CI, 12.2%-13.6%) of male siblings. When a female was associated with risk in the family, ASD was diagnosed in 7.6% (95% CI, 6.5%-8.9%) of female siblings and 16.7% (95% CI, 15.2%-18.4%) of male siblings.
Conclusions and Relevance These findings are in agreement with the higher rates of ASD observed among males than among females in the general population. Our study provides more specific guidance for the screening and counseling of families and may help inform future investigations into the environmental and genetic factors that confer risk of ASD.
“Association of Sex With Recurrence of Autism Spectrum Disorder Among Siblings” by Nathan Palmer, PhD; Andrew Beam, PhD; Denis Agniel, PhD; Alal Eran, PhD; Arjun Manrai, PhD; Claire Spettell, PhD; Gregory Steinberg, MD; Kenneth Mandl, MD; Kathe Fox, PhD; Stanley F. Nelson, MD; and Isaac Kohane, MD, PhD in JAMA Pediatrics. Published online September 25 2017 doi:10.1001/jamapediatrics.2017.2832