Is sex at birth a biological coin toss? Insights from a longitudinal and GWAS analysis

Some families consistently have offspring of only one sex, raising questions about whether sex at birth is truly random. This study investigated whether offspring sex follows a simple binomial distribution within families and identified maternal factors associated with unisexual sibships. We analyzed 58,007 US women with two or more singleton live births (146,064 pregnancies, 1956-2015). Offspring sex followed a beta-binomial rather than a simple binomial distribution, indicating that each family may have a unique probability of male or female births, akin to a weighted coin toss. Deviations from simple binomial distribution were more pronounced when we excluded each woman's last birth to reduce the influence of sex-based stopping behavior. After excluding the last birth, older maternal age at first birth was associated with higher odds of having offspring of only one sex. A genome-wide association study identified maternal SNPs linked to having female-only (NSUN6) and male-only (TSHZ1) offspring. Our findings suggest maternal factors influence offspring sex distributions.