🎉Immensely grateful and overwhelmingly joyful that my 1st first-author paper is out now in @BMCMedicine😁!!!🎉
This project started as my master’s thesis in @ImperialSPH with @VerenaZuber and @KTsilidis in the summer of 2020 😱!
Tweetorial 🧵⏬!
1/11
bmcmedicine.biomedcentral.com/articles/10.11…
🎯Aim: We wanted to examine and rank all 34 blood and urine biochemical biomarkers in the @uk_biobank for possible #causal relationships with #breastcancer liability in women.
2/11
🧮Methods: Since experimenting on biomarkers in human participants poses ethical and practical questions, we instead performed a method called Mendelian Randomisation (MR)🧬.
MR uses observational data👀 and an instrumental variable (IV) framework to infer causality.
3/11
🧮Methods: MR parallels a randomised controlled trial by leveraging the random inheritance of alleles at conception to investigate the causal relationship between the genetically predicted exposure and outcome.
4/11
🧮Methods: We used a variety of methods to identify and rank our biomarkers for causal relationships with breast cancer.
💻 Main = IVW MR
💻 Sensitivity = MR-Egger, Weighted median, MR-PRESSO
💻 Additional = multivariable and bidirectional MR
🥇 Ranking = MR-BMA
5/11
📊Data: We used publicly available summary-level genome-wide association study (GWAS) data on all 34 @uk_biobank biomarkers from the @bmneale lab and GWAS data on breast cancer from the Breast Cancer Association Consortium.
6/11
📈Results: We found likely causal associations between each of the following biomarkers and higher⬆️ or lower⬇️ overall breast cancer liability:
1⃣ Testosterone = ⬆️liability
2⃣ HDL cholesterol = ⬆️liability
3⃣ IGF-1 = ⬆️liability
4️⃣ Alkaline phosphatase (ALP) = ⬇️liability
7/11
💭Discussion: We corroborate existing findings, but the ALP finding is novel! We hypothesise that our ALP-associated gene variants are associated with an enzyme that breaks down oestrogen to the less potent oestrone, thus showing a reduced risk of breast cancer.
8/11
💭Discussion: One limitation is that we limited our sample to white-British women to avoid population stratification and cannot generalise to women of other ethnicities. Also, there is still the possibility of residual pleiotropy.
9/11
💭Discussion: Some strengths include our large sample of ~420,000 women! We avoid sex-specific effects, performed many methods to scrutinise our results, and included information on the relative importance of each biomarker.
10/11
🎇Finally, our work is licensed under the @creativecommons “Attribution license”, which allows anyone to read, copy, distribute and make derivative works, as long as the authors of the original work are cited – so feel free to share, use, and cite our work widely😊!
11/11
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