Thanks Chris!

As always, with huge thanks to many co-authors, particularly Laura Wittemans, Duncan Palmer, Triin Laisk, @ceclindgren.bsky.social 💫 And to the Rhodes Scholarship & Wellcome Trust for funding this work done at the Big Data Institute at the University of Oxford

… but in fantastic exome sequencing analyses led by Duncan Palmer we find that women in the UK Biobank carrying testosterone-lowering rare variants are at higher risk of infertility, so there is much more biology to find here [9/9]

We’re not quite done! We also conducted large-scale GWASs for reproductive hormones FSH, LH, oestradiol, progesterone, and testosterone in >200k men and women 🫂 but found no genetic correlation between infertility and hormone levels 🤯[8/9]

Overall, infertility is correlated with several health conditions… But there is no genetic correlation between obesity and any subtype of female infertility 🚫 – is it time we rethink weight loss as a cure-all strategy? 🤔 [7/9]

… highlighting the power of international genetic collaborations for biological discovery - which we did using wonderful biobanking data from the United Kingdom, Finland, Iceland, Denmark & Estonia [6/9]

And lest we forget about the men - we found two loci for male infertility, including ENO4 which is expressed in the testes and plays a role in sperm motility ♂️. The variant in ENO4 is only present in Estonia & Finland… [5/9]

Anovulatory infertility shares causal variants with PCOS at three loci, suggesting mechanisms of PCOS-driven infertility; and  is genetically correlated with twinning 👯, so genetically-informed treatments may target ovulation rate 💊 [4/9]

We saw high genetic correlation (71%) between infertility of “unknown” cause and endometriosis – is undiagnosed endometriosis responsible for many of these cases? 🤔 The average time to endometriosis diagnosis is >7 years from symptom onset, highlighting a huge unmet healthcare need! [3/9]

… EBAG9, which is a fantastic story of evolution – how do infertility risk-alleles persist in the population? We find recent directional selection (in the past 2000 years) at the EBAG9 locus, which confers immune benefits in mice 🤧, but also suppresses maternal immunity in pregnancy! [2/9]

We found 19 genetic loci for different types of female infertility, including 3 for infertility of unknown causes – WNT4 regulates female reproductive organ development in embryogenesis 🐣, TRHR is associated with primary ovarian insufficiency in mice 🐁, and … [1/9]