Mega Doctor News
by University of Chicago Medical Center
Newswise – Anyone who has a brother or sister knows that siblings raised under the same roof can show stark dissimilarities when it comes to everything from favorite colors to food allergies. For Andrey Rzhetsky, PhD, the Edna K. Papazian Professor of Medicine at the University of Chicago, those everyday observations turned into a scientific hunch.
“I have casually observed a lot of differences among sets of siblings in both my research and my own family, such as older siblings often being overachievers,” he said. “I came to wonder if diseases might also differ across siblings. Fortunately, we have the data to tackle this question.”
The resulting study, published in Nature Health, suggests that some of those differences run deeper than personality. Rzhetsky’s team analyzed anonymized insurance claims from over 5 million American two-child families and found that the order in which a child is born into a family is meaningfully associated with the diseases they are likely to develop later in life. Among 418 conditions the researchers examined, 150 showed statistically significant links to birth order, with firstborns more prone to neurodevelopmental disorders and allergies and second-borns more prone to substance use disorders, migraines, and certain gastrointestinal and infectious conditions.
The findings, drawn from one of the largest sibling datasets ever assembled, suggest that early-life environment leaves a durable fingerprint on adult health. This doesn’t mean anyone is destined to get sick because of where they fall in the family lineup, but the knowledge could help inform preventative care and shed light on health trends.
An enormous natural experiment
As someone who studies complex human phenotypes on a large scale, Rzhetsky says siblings offer a rare gift to researchers: a built-in control group.
“Genetically, two siblings have the same probability of getting genes from each parent,” he explained. “It’s kind of a natural randomization process.”
That randomization allowed the team, led by first author Benjamin Kramer — a summer research student in Rzhetsky’s lab at the time — to isolate and closely scrutinize an array of environmental influences.
The researchers ran two parallel analyses: a between-family comparison of 1.6 million matched pairs and a within-family comparison across all 5.1 million families, controlling for parental age, sex, and the gap between births. Both approaches produced results that pointed in the same direction.
Firstborns showed elevated odds of being diagnosed with autism, ADHD, Tourette’s syndrome, obsessive-compulsive disorder, depression, and anxiety, as well as asthma, allergic rhinitis, food allergies, and acne. In contrast, second-born siblings carried higher odds of substance use disorders, gastritis, duodenitis, migraines, shingles, biliary tract disease, and kidney infections. The overall split was surprisingly even: 79 conditions were more likely to appear in firstborns, while 71 favored second-borns.
Importantly, Rzhetsky emphasized, this doesn’t mean one sibling is doomed to encounter more health issues.
“It’s not that order of birth makes a person sicker,” he said. “Just the probability of what hits first changes.”
The mystery of the age gap
One of the study’s most intriguing findings involves the space between siblings. Shorter gaps between births were associated with reduced risk of several conditions, particularly neuropsychiatric diagnoses in older siblings, and allergies and asthma in both. That pattern hints at a biological explanation Rzhetsky finds especially compelling.
“We can’t yet prove this hypothesis, but we suspect the exchange of microbiome between two siblings may play a role,” he said. “It would make sense for the microbiome exchange to be more protective when the age gap is small.”
The theory aligns with the long-standing “hygiene hypothesis,” which proposes that early exposure to a diverse array of microbes helps train the developing immune system. A younger sibling arriving soon after the first may both contribute to and benefit from a richer microbial mix in the household.
Future studies may explore sibling microbiomes and other possible explanations, including subtle differences in parental attention, diagnostic timing, and the biology of successive pregnancies.
Potential to inform proactive care
Rzhetsky says that for now, parents and patients shouldn’t read too much into these results when considering their own families’ health. The associations are real but modest at the individual level, and birth order is only one thread in a very tangled web of disease risk factors. Still, he sees opportunities for practical implications on a broader level.
“First and second siblings might benefit from different prophylaxis,” he suggested. “Physicians may want to watch different populations more closely for different things.” For example, a pediatrician who knows a whole family could tailor screening or preventive advice according to birth order, watching more closely for allergies in a first child, or for signs of gastrointestinal disorders in a second.
The team is already extending the work internationally, examining national health data from other countries to see if the core findings are replicated. Rzhetsky’s longer-term hope is to move from observing patterns to identifying mechanisms — to figure out how and why being born first, or second, or three years after a sibling instead of one, nudges the body down subtly different paths.
“Birth order and disease risk across the human phenome” was published in Nature Health in August 2026. Co-authors are Benjamin Kramer, Steven A. Kushner & Andrey Rzhetsky.
