Why Is Autism More Common in Males?
Talukdar investigates how X chromosome genes reduce female risk—and potentially protect against other developmental disorders
When Maya Talukdar’s mother was diagnosed with a rare cancer-like disease called amyloidosis, she contacted research labs near her hometown of Buffalo, New York, to see how she could contribute to fighting it.
“We were hitting up against the limit of our knowledge of the disease. Our doctors were all amazing, and we had a lot of family support, and still I was aware of how much no one could really answer,” she recalled. “I wanted to see if there was a way—I guess in a very naive way—that I could contribute to some of this work. So, I joined a lab at the University at Buffalo and got totally hooked on biomedical research.”
Talukdar received her PhD in bioinformatics and integrative genomics from Harvard Griffin GSAS in November 2025, and is now completing her MD at Harvard Medical School (HMS) through the joint Harvard/MIT MD-PhD program. Today she brings her passion for science to research that explores how sex-based genetic differences might drive disparities in rates of autism, heart disease, and potentially, a raft of other disorders.
Pinpointing the Female Protective Effect
Many medical conditions affect men and women at strikingly different rates. Autism is four times more common in men, while Alzheimer’s disease affects twice as many women. Gender stereotypes can impede symptom recognition and reporting, which contributes greatly to these disparities. But social factors do not fully account for the gaps, suggesting that biological sex differences between males and females may also play a role.
Talukdar’s dissertation research explores the genetic underpinnings of females’ reduced autism risk, which geneticists have termed the female protective effect (FPE).
“Females who have autism tend to have more mutations than males who have autism, which suggests that females require more genetic risk to manifest autism,” Talukdar explained. “Another way of thinking about this is that females are somehow protected from the genetic risk associated with the condition.”
While the FPE is well-documented, scientists still struggle to explain exactly what causes it. Talukdar’s breakthrough, with the help of her lab mates and advisors, was to pinpoint a gene on the X chromosome that appears to contribute to this protection.
“There’s one particular gene that’s expressed from the inactive X chromosome, ZFX, which . . . appears to increase the expression of many genes that are usually decreased in autism,” Talukdar said. “The idea is that because females have higher expression of ZFX at baseline, they have higher expression of many genes that are often perturbed in autism. Which means that, even if you end up decreasing their expression a little bit, a girl with an autism-associated mutation is still better able to buffer that mutation as compared to a boy.”
The idea is that because females have higher expression of [the inactive X chromosome] ZFX at baseline, they have higher expression of many genes that are often perturbed in autism. Which means that, even if you end up decreasing their expression a little bit, a girl with an autism-associated mutation is still better able to buffer that mutation as compared to a boy.
—Maya Talukdar
According to her co-advisor, Professor Christopher Walsh of HMS, Talukdar’s work not only helps solve the genetic puzzle of the FPE but may also facilitate impactful new clinical interventions.
“This work reveals an unexpected interconnectedness between diverse genetic causes of autism, but [it] also suggests new ways of directing therapies toward these X chromosome genes that might help affected autistic children,” he said.
Implications Beyond Autism
While most scholars only study the female protective effect as it pertains to autism, Talukdar sees a bigger story. She hypothesizes that the FPE might explain why several other disorders diagnosed in early childhood, such as congenital heart disease and certain gastrointestinal (GI) disorders, disproportionately impact males.
“This framing that the FPE is only about autism is not the right way to look at it, because we see it in all these other disorders,” Talukdar said. “If you're looking for an explanation for the FPE, it can't just be about the brain. It has to explain what's going on in the heart, and it has to explain what's going on in the GI tract.”
Alongside her co-advisor, MIT Professor of Biology David Page, Talukdar re-analyzed existing genetic data on pediatric disorders to test this hypothesis. The resulting paper, recently published in Nature Genetics, finds similar FPEs in a variety of other genetic disorders.
This framing that the FPE (female protective effect) is only about autism is not the right way to look at it, because we see it in all these other disorders. If you're looking for an explanation for the FPE, it can't just be about the brain. It has to explain what's going on in the heart, and it has to explain what's going on in the GI tract.
—Maya Talukdar
Professor Among Students
In addition to her FPE research, Talukdar has also proposed a new explanation for Alzheimer's disease, identified molecular changes in epilepsy, and investigated sex differences in brain cancer and cardiac metabolism—all while simultaneously pursuing her medical degree. Much of this work has been published or is forthcoming in journals such as PNAS, Circulation, and Cell.
Page says she operates more like a “professor among students” than a graduate student, equating her portfolio to nearly two dissertations’ worth of research.
“Maya is a very remarkable student who, from my first meetings with her, was operating at an unusually high level,” he said. “She has the appetite for deeply immersing herself in multiple perspectives and understanding the importance of those multiple perspectives in framing and approaching a question. Even among senior colleagues, that is a fairly unusual trait.”
Talukdar has also gone above and beyond as a mentor for her fellow graduate students, voluntarily serving as a teaching assistant nearly every term. She credits this teaching experience with keeping her passion for medicine and science alive, even when she faced setbacks in the lab.
“Often, I taught first-year students, and they had just come to campus. They were so excited! It makes you remember what drives you to science or medicine,” she said. “Sometimes I think when things are tough in lab, our solution is to put our heads down and just spend more time on it. But I've found that taking targeted breaks from lab to do other things that fill your cup really can help you have a better experience.”
[Talukdar’s] work reveals an unexpected interconnectedness between diverse genetic causes of autism, but [it] also suggests new ways of directing therapies toward these X chromosome genes that might help affected autistic children.
—Harvard Medical School Professor Christopher Wolf
Bridging Medicine and Research
Talukdar has been passionate about biomedical research since her mother’s amyloidosis diagnosis prompted her to join a lab in high school. She continued down this path as an undergraduate at Columbia University, studying computational biology with a focus on research—not medicine. But when it came time for graduate school, she realized that research alone would not be enough.
“Research was sort of my first love, but medicine, or caring for others, fulfilled more of a spiritual or personal need for me,” she said. “So when I thought about next steps, I thought about MD-PhD programs, and I came to Harvard.”
She learned that sex-based genetic difference might play a role in the rates at which men and women develop certain diseases during a guest lecture by Page. The idea immediately captivated her.
“One of his first slides was going through different diseases and talking about how sex biased they are, and he put up autism right away, which caught my attention,” Talukdar said. “He was talking about how there could be fundamental differences, down to how we modify, transcribe, and translate our genome, between males and females. Which totally blew my mind.”
Inspired by the lecture, Talukdar convinced Page to co-advise her dissertation alongside Walsh, an expert in neurogenetics with a deep understanding of autism. The two scientists had never collaborated before, but they saw promise in Talukdar’s idea. Pooling their collective expertise, she began exploring how sex chromosomes might relate to autism.
“It was a project that could only have happened having both of their expertise,” she said. “I think the way they've supported me the most as a scientist is giving me tremendous intellectual freedom to pursue what I'm interested in.”
After finishing her MD, Talukdar hopes to continue her medical education with residency training that combines her interests in women’s health and pediatrics. As gene-based medical treatments become more feasible, she believes her research experience in genetics will be a clinical asset.
“It’s this completely new era where we’re starting to think about what genetic interventions could look like,” she said. “I'm hoping in the future that I can be someone who helps bridge these two worlds.”
Talukdar’s mother is one beneficiary of rapidly advancing medical treatments driven by innovative science. Ten years into remission, her doctors assure her that if the disease were to return, they now have much stronger tools to fight it.
“I think that speaks to how quickly science can change medicine, and the personal impact of the medicine,” Talukdar reflected.
Maya Talukdar’s research was supported by a National Institutes of Health T32 training grant (GM144273).
