Largest study to date reveals gender-specific risk of autism occurrence among siblings

September 25, 2017
Credit: CC0 Public Domain

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 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 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 Harvard Medical School. "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 Harvard Medical School.

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 with autism—the odds are still about five to one that the 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 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 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.

Explore further: Autism risk in younger children increases if they have older sibling with disorder

Related Stories

Autism risk in younger children increases if they have older sibling with disorder

August 5, 2016
A new Kaiser Permanente study found that the risk of younger siblings developing an autism spectrum disorder is 14 times higher if an older sibling has ASD. The study, which was published today in Journal of Developmental ...

Does having a sibling with autism affect a child's language and motor skills?

July 19, 2017
A review of published studies suggests that infants who have siblings with autism spectrum disorder may have less advanced linguistic and motor skills than siblings of children with typical development.

New study shows boys will be boys—sex differences aren't specific to autism

June 9, 2015
There are more boys than girls diagnosed with autism spectrum disorder (ASD). Now, a study led by a University of Miami (UM) researcher shows that behaviors relevant to autism are more frequently observed in boys than in ...

In autism, the social benefits of being a girl

February 9, 2016
Infant girls at risk for autism pay more attention to social cues in faces than infant boys, according to a Yale School of Medicine study—the first one known to prospectively examine sex-related social differences in at-risk ...

Risk of autism among younger siblings of a child with autism much greater than previously reported

August 15, 2011
Autism Speaks, the world's largest autism science and advocacy organization, joined in announcing significant findings from the largest known study of younger siblings of children who had a verified diagnosis of autism spectrum ...

Recurrence risk for autism spectrum disorders examined for full, half siblings

August 19, 2013
A Danish study of siblings suggests the recurrence risks for autism spectrum disorders (ASDs) varied from 4.5 percent to 10.5 percent depending on the birth years, which is higher than the ASD risk of 1.18 percent in the ...

Recommended for you

Video game improves balance in youth with autism

November 21, 2017
Playing a video game that rewards participants for holding various "ninja" poses could help children and youth with autism spectrum disorder (ASD) improve their balance, according to a recent study in the Journal of Autism ...

Potential new autism drug shows promise in mice

November 14, 2017
Scientists have performed a successful test of a possible new drug in a mouse model of an autism disorder. The candidate drug, called NitroSynapsin, largely corrected electrical, behavioral and brain abnormalities in the ...

Relational factors in music therapy can contribute to positive outcome for children with autism

November 6, 2017
It might not surprise that good relationships create good outcomes, as meaningful relational experiences are crucial to all of us in our everyday life. However, the development of a relationship with a child with autism may ...

In autism, too many brain connections may be at root of condition

November 2, 2017
A defective gene linked to autism influences how neurons connect and communicate with each other in the brain, according to a study from Washington University School of Medicine in St. Louis. Rodents that lack the gene form ...

New autism study a "shocking wake-up call" for society, say academics

October 23, 2017
People who show characteristics of autism are more at risk of attempting suicide, according to a Coventry University study whose results are being presented to a United States federal advisory committee tomorrow.

Signaling pathway may be key to why autism is more common in boys

October 17, 2017
Researchers aiming to understand why autism spectrum disorders (ASD) are more common in boys have discovered differences in a brain signaling pathway involved in reward learning and motivation that make male mice more vulnerable ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.