The genetic architecture of and evolutionary constraints on the human pelvic form.

Human pelvic evolution following the human-chimpanzee divergence is thought to result in an obstetrical dilemma, a mismatch between large infant brains and narrowed female birth canals, but empirical evidence has been equivocal. By using deep learning on 31,115 dual-energy x-ray absorptiometry scans from UK Biobank, we identified 180 loci associated with seven highly heritable pelvic phenotypes. Birth canal phenotypes showed sex-specific genetic architecture, aligning with reproductive function. Larger birth canals were linked to slower walking pace and reduced back pain but increased hip osteoarthritis risk, whereas narrower birth canals were associated with reduced pelvic floor disorder risk but increased obstructed labor risk. Lastly, genetic correlation between birth canal and head widths provides evidence of coevolution between the human pelvis and brain, partially mitigating the dilemma. Editor's summary: The obstetrical dilemma stems from a conflict between the optimal pelvic structure for bipedalism and what is required for successfully birthing infants with larger brains than previous hominins. However, the data required to test this theory have not been available. Xu et al. used the UK Biobank to disentangle the genetic basis of pelvic morphology. They found 180 genome sites associated with seven pelvic proportion phenotypes, as well as genetic correlations between pelvic proportions and traits such as osteoarthritis, walking speed, and back pain, giving insight into facets of the obstetrical dilemma. —Corinne Simonti INTRODUCTION: Human pelvic shape has undergone significant evolutionary change since the divergence from the chimpanzee lineage. This transformation involved the reduction of pelvic canal dimensions to support bipedal locomotion. At the same time, human brain size also expanded significantly, which gave rise to the obstetrical dilemma, a hypothesis that highlights the mismatch between the large brain size of infants and the narrowed female birth canal. Initially proposed in the 1960s, empirical support for this classic hypothesis has been equivocal, largely owing to limitations in sample size and a lack of appropriate types of data. RATIONALE: By using a deep learning model, we extracted a set of seven pelvic phenotypes, including three measures of the birth canal, from dual-energy x-ray absorptiometry (DXA) scans of 31,115 individuals from the UK Biobank. To elucidate the genetic underpinnings of pelvic morphology, we conducted a genome-wide association study (GWAS) on these seven pelvic traits and combined these results with multiple physiological and clinical outcomes related to childbirth, locomotion, and pelvic floor function. We also tested relevant evolutionary hypotheses to further explore potential evolutionary responses to alleviate the obstetrical dilemma. RESULTS: The results revealed that all pelvic proportions are highly heritable (~32 to 48%), and a GWAS of these traits identified 180 independent loci. Unlike other skeletal proportions, such as long bone lengths, the subpubic angle, which determines the size of the birth canal, shows an estimated genetic correlation between sexes significantly less than 1, consistent with sex-specific reproductive functions. Additionally, although pelvic proportions display left-right asymmetry, this asymmetry is not heritable and is instead associated with handedness. We conducted phenotypic and genetic association analyses to link pelvic proportions to three facets of the obstetrical dilemma. For childbirth-related outcomes, narrower birth canal phenotypes were linked to an increased risk of emergency cesarean sections and obstructed labor owing to insufficient dilation but not obstruction due to fetal positioning, suggesting that childbirth imposes selective pressure to widen the birth canal. Conversely, larger birth canals were associated with reduced walking pace and a decreased risk of back pain but an increased risk of hip osteoarthritis, suggesting that lifelong effects of birth canal width reduction on locomotor efficiency are mixed. However, larger birth canal width was significantly associated with an increased risk of genital prolapse and incontinence, suggesting that pelvic floor disorders impose additional constraints. Lastly, we investigated whether the dilemma might have been alleviated through evolution. In line with recent evidence from great apes, we found no evidence for an association between pelvic proportions and gestational duration, suggesting that there has not been selection for earlier childbirth. Instead, we observed that infant and adult head widths were genetically correlated with maternal birth canal widths. CONCLUSION: Our study provides fresh insights into a 60-year-old debate in human evolution. Beyond pressures imposed by childbirth, as initially proposed by the obstetrical dilemma hypothesis, our findings suggest that, rather than just locomotion, pelvic floor health may have played a significant role in reducing birth canal width in our transition to bipedalism. Our observed genetic correlation between birth canal width and infant and adult head width provides support for the coevolution of the human brain and pelvis. Understanding the genetic basis of human pelvic proportions and how they impact locomotion, pelvic floor function, and childbirth.: (A) Measurement of pelvic proportions using deep learning–based landmark estimation on 31,115 DXAs. (B) Location of loci that localize to a single protein-coding gene associated with various pelvic proportions colored according to the scheme in (A). (C) Multiple lines of evidence supporting and expanding on the obstetrical dilemma hypothesis. OA, osteoarthritis. [Figure created with BioRender.com] [ABSTRACT FROM AUTHOR]