Cecilia Lindgren

So excited to give a talk at #ESHG2025! ✨

I presented our work demonstrating that individuals whose phenotype deviates from genetic expectation are enriched for rare damaging variants.

This has implications for:
- Screening of rare disorders 🔎
- Target discovery 💊
- Improving trait prediction 📈

Great week in SF at #JPM2025 with @ceclindgren.bsky.social chatting partnerships and impact in women’s health. Aneira Health was of course the toast of the town! More broadly, amazing energy in this space - big increase since last year even! 🚀

The ability to saying yes is not a random feature 🍀✨

Road blocked by crushed wall as Storm Darragh fells tree Storm Darragh has blocked an Oxford road after a fallen tree smashed the nearby wall.

Ett träd 🌳 föll över vägen så bussen åkte runt för att få hem oss - ovanligt www.oxfordmail.co.uk/news/2477940...

Genome-wide analyses identify 21 infertility loci and over 400 reproductive hormone loci across the allele frequency spectrum Genome-wide association studies (GWASs) may help inform treatments for infertility, whose causes remain unknown in many cases. Here we present GWAS meta-analyses across six cohorts for male and female infertility in up to 41,200 cases and 687,005 controls. We identified 21 genetic risk loci for infertility (P≤5E-08), of which 12 have not been reported for any reproductive condition. We found positive genetic correlations between endometriosis and all-cause female infertility (rg=0.585, P=8.98E-14), and between polycystic ovary syndrome and anovulatory infertility (rg=0.403, P=2.16E-03). The evolutionary persistence of female infertility-risk alleles in EBAG9 may be explained by recent directional selection. We additionally identified up to 269 genetic loci associated with follicle-stimulating hormone (FSH), luteinising hormone, oestradiol, and testosterone through sex-specific GWAS meta-analyses (N=6,095-246,862). While hormone-associated variants near FSHB and ARL14EP colocalised with signals for anovulatory infertility, we found no genetic correlation between female infertility and reproductive hormones (P>0.05). Exome sequencing analyses in the UK Biobank (N=197,340) revealed that women carrying testosterone-lowering rare variants in GPC2 were at higher risk of infertility (OR=2.63, P=1.25E-03). Taken together, our results suggest that while individual genes associated with hormone regulation may be relevant for fertility, there is limited genetic evidence for correlation between reproductive hormones and infertility at the population level. We provide the first comprehensive view of the genetic architecture of infertility across multiple diagnostic criteria in men and women, and characterise its relationship to other health conditions. ### Competing Interest Statement L.B.L.W. is currently employed by Novo Nordisk Research Centre Oxford but, while she conducted the research described in this manuscript, was only affiliated to the University of Oxford. V.S., G.T., H.H., I.J., and K.S. are employees of deCODE genetics, a subsidiary of Amgen. C.M.L. reports grants from Bayer AG and Novo Nordisk and has a partner who works at Vertex. The other authors declare no conflicts of interest. ### Funding Statement S.S.V. is supported by the Rhodes Scholarships, Clarendon Fund, and the Medical Sciences Doctoral Training Centre at the University of Oxford. L.B.L.W. was supported by the Wellcome Trust. B.M.J. is funded by an Medical Research Council (MRC) Clinical Research Training Fellowship (CRTF) jointly supported by the UK MS Society (B.M.J. grant reference: MR/V028766/1). A.P. is supported by Alma and K.A. Snellman Foundation. Genes & Health is/has recently been core-funded by Wellcome (WT102627, WT210561), the Medical Research Council (UK) (M009017, MR/X009777/1, MR/X009920/1), Higher Education Funding Council for England Catalyst, Barts Charity (845/1796), Health Data Research UK (for London substantive site), and research delivery support from the NHS National Institute for Health Research Clinical Research Network (North Thames). A.E. and D.A.L contributions are supported by the UK Medical Research Council (MC\_UU\_00032/05) and the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreements No 101021566). Genes & Health is/has recently been funded by Alnylam Pharmaceuticals, Genomics PLC; and a Life Sciences Industry Consortium of Astra Zeneca PLC, Bristol-Myers Squibb Company, GlaxoSmithKline Research and Development Limited, Maze Therapeutics Inc, Merck Sharp & Dohme LLC, Novo Nordisk A/S, Pfizer Inc, Takeda Development Centre Americas Inc. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). Genome-wide genotyping data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. C.M.L. is supported by the Li Ka Shing Foundation, NIHR Oxford Biomedical Research Centre, Oxford, NIH (1P50HD104224-01), Gates Foundation (INV-024200), and a Wellcome Trust Investigator Award (221782/Z/20/Z). The research was supported by the Wellcome Trust Core Award Grant Number 203141/Z/16/Z with additional support from the NIHR Oxford BRC. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was conducted using data from seven research studies, each with separate ethics approval. 1. UK Biobank has approval from the North West Multi-centre Research Ethics Committee (MREC) as a Research Tissue Bank (RTB) approval. 2. Copenhagen Hospital Biobank is classified as a biobank for future research. It is part of the Danish National Biobank and has been approved by the Danish Data Protection Agency (general approval number 2012-58-0004, and local number: RH-2007-30-4129/I-suite 00678). The Danish Blood Donor Study was approved by the Central Denmark (1-10-72-95-13) and Zealand (SJ-740) Regional Committees on Health Research Ethics and the Data Protection Agency (P-2019-99). The DBDS GWA study was approved by the Danish National Committee on Health Research Ethics (1700407). SCANDAT was approved by the Data Protection Agency (2008-54-0472). The DBDS was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. 3. Genes & Health operates under ethical approval, 14/LO/1240, from London South East NRES Committee of the Health Research Authority, dated 16 September 2014. 4. The activities of the Estonian Biobank are regulated by the Human Genes Research Act, which was adopted in 2000 specifically for the operations of the EstBB. Individual level data analysis in the EstBB was carried out under ethical approval 1.1-12/624 from the Estonian Committee on Bioethics and Human Research (Estonian Ministry of Social Affairs), using data according to release application 3-10/GI/10790 from the Estonian Biobank. 5. Patients and control subjects in FinnGen provided informed consent for biobank research, based on the Finnish Biobank Act. Alternatively, separate research cohorts, collected prior the Finnish Biobank Act came into effect (in September 2013) and start of FinnGen (August 2017), were collected based on study-specific consents and later transferred to the Finnish biobanks after approval by Fimea (Finnish Medicines Agency), the National Supervisory Authority for Welfare and Health. Recruitment protocols followed the biobank protocols approved by Fimea. The Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa (HUS) statement number for the FinnGen study is Nr HUS/990/2017. The FinnGen study is approved by Finnish Institute for Health and Welfare (permit numbers: THL/2031/6.02.00/2017, THL/1101/5.05.00/2017, THL/341/6.02.00/2018, THL/2222/6.02.00/2018, THL/283/6.02.00/2019, THL/1721/5.05.00/2019 and THL/1524/5.05.00/2020), Digital and population data service agency (permit numbers: VRK43431/2017-3, VRK/6909/2018-3, VRK/4415/2019-3), the Social Insurance Institution (permit numbers: KELA 58/522/2017, KELA 131/522/2018, KELA 70/522/2019, KELA 98/522/2019, KELA 134/522/2019, KELA 138/522/2019, KELA 2/522/2020, KELA 16/522/2020), Findata permit numbers THL/2364/14.02/2020, THL/4055/14.06.00/2020, THL/3433/14.06.00/2020, THL/4432/14.06/2020, THL/5189/14.06/2020, THL/5894/14.06.00/2020, THL/6619/14.06.00/2020, THL/209/14.06.00/2021, THL/688/14.06.00/2021, THL/1284/14.06.00/2021, THL/1965/14.06.00/2021, THL/5546/14.02.00/2020, THL/2658/14.06.00/2021, THL/4235/14.06.00/2021, Statistics Finland (permit numbers: TK-53-1041-17 and TK/143/07.03.00/2020 (earlier TK-53-90-20) TK/1735/07.03.00/2021, TK/3112/07.03.00/2021) and Finnish Registry for Kidney Diseases permission/extract from the meeting minutes on 4th July 2019. 6. Ethical approval for the study was obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC) Ethics and Law Committee and the Local Research Ethics Committees. 7. The deCode Genetics study was approved by the Icelandic National Bioethics Committee (approval no. VSN-19-023). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Cohorts may be contacted individually for access to raw data. Summary statistics for all phenotypes will be made available through the GWAS Catalog upon publication. All code used in this study will be made available through GitHub upon publication.

Infertility affects 1 in 6 couples across the globe, but its cause remains unknown in over 30% of cases 😔 In our latest work in the Lindgren group, we discover rare and common genetic variants associated with infertility - www.medrxiv.org/content/10.1... My first bsky thread below!⬇️

a beach with a lot of people on it ALT: a beach with a lot of people on it

We are HIRING a postdoc! Are you into cardiovascular genomics? Does gene discovery and rare variants get you out of bed!? OMG, me too! Unfortunately i can't apply for this role, but YOU CAN! Come join our research lab at @garvaninstitute.bsky.social Sydney 🇦🇺 #genesky www.seek.com.au/Garvan-Insti...

This one I'm very proud of: we identified a common genetic variant 🧬 that protects 5-fold from neonatal jaundice (replicated in different ancestries) which increases UGT1A1 (main bilirubin enzyme) expression in the gut, but not in the liver! 🖥️🧪🧬 A lot more here:

www.nature.com/articles/s41...

UK commuters: tell us how you have been affected by the National Rail systems fault We would like to hear how your train journey has been affected by the ‘nationwide fault’ Network Rail has said a “nationwide” fault with the communication system used between train drivers and signallers could cause disruption across the network. Trains…

UK commuters: tell us how you have been affected by the National Rail systems fault

@kasperlage?

National Rail warns of widespread disruption after communications system fault Trains having to start their journeys later and some may be subject to cancellations or alterations

www.theguardian.com/uk-news/2024...

a blue and white train with a sign that says ' amsterdam ' on it ALT: a blue and white train with a sign that says ' amsterdam ' on it

This country needs to sort out it’s train system - urgently - for a whole range of reasons #canwepleaseemulateourfriendsinjapan

Applications are now OPEN for the 2025 Human Genetics and Genomics GRC and GRS!! 🎉 🧬

📅 GRS: July 5-6, 2025
📅 GRC: July 6-11, 2025
📍 Portland, Maine

@calliao.bsky.social and I are co-chairs for the GRS, with Shamil Sunyaev and @eimearekenny.bsky.social as the GRC chairs 👀

Links to apply below 👇

Biology of Genomes Cold Spring Harbor Laboratory Meetings & Courses -- a private, non-profit institution with research programs in cancer, neuroscience, plant biology, genomics, bioinformatics.

Biology of Genomes 2025 is coming up:
- meeting dates: May 6 - 10, 2025
- abstract deadline: Feb 14, 2025
We hope to see you there for another great meeting with a fantastic speaker lineup!

meetings.cshl.edu/meetings.asp...

Did you know that Germany has its own large-scale population-based biobank?

The German National Cohort or NAKO❗

If not, let me tell you why👇

Compare it to @ukbiobank.bsky.social - which is democratized and available ✨🍀

Human adipose depots’ diverse functions and dysregulations during cardiometabolic disease - npj Metabolic Health and Disease npj Metabolic Health and Disease - Human adipose depots’ diverse functions and dysregulations during cardiometabolic disease

Our latest review in NJP Metabolic Health and Disease: eur02.safelinks.protection.outlook.com?url=https%3A...

A pitch for the creativity and innovation that discovery research offers and the humility researchers need to have for exploring impact or their work - impact for individuals and societies - impact for empowering, accelerating good outcomes - for driving us forward to betterment a

a thankful for you greeting card with a wreath of leaves and a pumpkin ALT: a thankful for you greeting card with a wreath of leaves and a pumpkin

Two nuggets we all do well contemplating are

1. Master your circumstances or they will master you
2. The surest sign of wisdom is constant cheerfulness
3. Positive polite persistence conquers all

#PPP #wearestrongertogether #generositywins

Genetic basis of early onset and progression of type 2 diabetes in South Asians Nature Medicine - In a cohort of 50,556 South Asian individuals, partitioned polygenic scores helped identify genetic susceptibility to insulin deficiency and unfavorable fat distribution as key...

It’s a big day for @genesandhealth.bsky.social @samcbhodgson.bsky.social @moneeza-ks.bsky.social Genes & Health, with @ Sam Hodgson, Moneeza Kalhan Siddiqui and I, as we publish our paper rdcu.be/d1vj0 on the genetic basis of #type2diabetes & #gestationaldiabetes (#T2D and #GDM) in south Asians. A🧵

Lets see if BlueSky can be as helpful as Old School Twitter.

I'm looking for advocates of Administrative Data Access and Linkage across the EU 🇪🇺

Tell me who is making administrative data access happen in 🇮🇹🇪🇸🇩🇰🇸🇪🇫🇮🇨🇿🇸🇮🇸🇰🇭🇷🇧🇪🇩🇪🇵🇱🇧🇬🇷🇴🇲🇹🇭🇺🇬🇷

This is often unsung work and they don't toot their own horns.

RP 🙏

Here is to hoping 🍀✨

😂

At twitter you tweet. X you … tweet. Bluesky you …. beep? Is there a verb for Bluesky posting? Paging @jay.bsky.team

Results from British Academy's experiment of randomized awarding of research grants to proposals which all have passed a high quality threshold indicates that random selection increases diversity dramatically.

#academicsky @academic-chatter.bsky.social 🧪

www.thebritishacademy.ac.uk/news/promisi...

Gallup Cigarette Smoking Among U.S. Adults Near Record Low Have you, yourself, smoked any cigarettes in the past week?

US adults who smoke

Ie people I follow = follows 🤩✨

Does anyone know a shortcut for importing my follows into this amazing space from another formerly blue space - or do I need to sit and find everyone again 🚀🤞🍀✨

Living fearlessly with fear ✨ #onwards #ppp