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Veera Rajagopal  Profile picture
Veera Rajagopal 
@doctorveera
🇮🇳 MBBS, MD, 🇩🇰 PhD | 🧬 Scientist @ 🇺🇸 Regeneron | Translating genetic insights into life-saving medicines | Weekly thoughts @ https://t.co/dTItNQxuMp
Feb 15 • 4 tweets • 2 min read
Someone used DALL-E to create gobbledygook scientific figures and submitted them to Frontiers Journal. And guess what? The editor published it. LOL
frontiersin.org/articles/10.33…



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Image @MicrobiomDigest You might like this 😅
Jan 15 • 7 tweets • 1 min read
A beautiful study by Nivard et al. on the direct and indirect genetic effects on school achievement shows that the indirect effects act primarily via dynastic effects rather than genetic nurture.
nature.com/articles/s4156… An indirect effect is the association of genetic variants in parents (that are not transmitted to their offspring) with the phenotype in the offspring, which is believed to be mediated via genetic nurture.
May 22, 2023 • 4 tweets • 2 min read
GWAS of structural variants in 5213 cases and 4132 controls identifies a common 309bp intronic deletion in TPCN1 as a new risk variant for Lewy body dementia.

Kaivola et al. @CellGenomics
cell.com/cell-genomics/… Image This locus has been previously linked to Alzheimer's and Parkinson's via SNP-based GWASs. While the Alzheimer's SNP effect sizes at this locus were concordant with LBD effect sizes, the Parkinson's weren't. It's possible this deletion is the causal variant. Image
Mar 5, 2023 • 5 tweets • 2 min read
One of the interesting findings in the recent GWAS of number of children ever born (NEB) is the discovery of a possible role of pigmentation gene MC1R (melanocortin 1 receptor) in reproduction. While MC1R locus did not reach genome-wide significance, a gene-based test using only non-synonymous variants showed a significant association between MC1R and NEB with the effect in women > men.
Feb 22, 2023 • 16 tweets • 4 min read
While I appreciate the sentiment, I am not a fan of such blind rules. Let me start with a 🧵 of some major human genetic discoveries (many translated to therapeutics) made with very few samples.
1. Association of complement factor H with AMD was discovered with mere 96 cases and 50 controls. Today many drug pipelines are in development based on this discovery.
science.org/doi/10.1126/sc…
Feb 20, 2023 • 25 tweets • 7 min read
Beautiful story of how human population genetic and proteomic studies have led to the discovery of SVEP1 as the natural ligand of the receptor PEAR1. It's been a while since I read such a fantastic paper. 🧵
nature.com/articles/s4146… I am big fan of GWAS of molecular traits as they often reveal clear and interpretable cis and trans signals reiterating the known biology of the trait.
Jan 12, 2023 • 8 tweets • 3 min read
My first favourite GWAS of the year.
Here the authors derived >3k cellular morphological traits using microscopic images of iPSCs from 297 donors and studied their associations with common and rare variants. Amazing
biorxiv.org/content/10.110…
@soumya_boston @DrAnneCarpenter In the rare variant analysis, the authors discovered three beautiful associations where pLOF burden results in big changes in cellular morphology.
Jan 10, 2023 • 24 tweets • 5 min read
Better late than never. Happy and relieved to share a final published version of one of my PhD projects in which we uncovered a fascinating genetic link between language ability, psychiatric risk and creativity. 🧵
nature.com/articles/s4159… Endophenotypes are at the heart of human genetics research. They not only help discover disease genes, but they can also inform about the disease's pathophysiology, signs, symptoms etc.
Jan 8, 2023 • 4 tweets • 2 min read
GWAS of obstructive sleep apnea (OSA). Just looking at this plot one can easily tell what is the major risk factor of OSA.
medrxiv.org/content/10.110… Image The FTO locus is entirely driven by the BMI of the participants. The locus disappears after adjusting for BMI. Similar to how the CHRNA5 locus in the GWAS of lung cancer is entirely driven by smokers.
Dec 31, 2022 • 16 tweets • 7 min read
Here it is. The final GWAS story for the year! I look back at all the exciting stories I tweeted in the last 12 months. It has been truly an amazing year. I'll highlight a selected few in this thread. 🧵
gwasstories.substack.com/p/2022-roundup… 1. Ancient DNA research stole the show this year with the Nobel Prize announcement and this mind-blowing paper on the positive selection driven by the Black Death.
Dec 22, 2022 • 12 tweets • 3 min read
Agouti gene (Asip) is the first obesity gene to be discovered in 1992 in agouti mice--a fat yellow mice with a mutation that reprograms a skin specific protein to express throughout the body. However, no mutations in this gene has been reported in humans since 1992. 🧵 Thirty years later, now scientists have encountered the first human patient who is a near phenocopy of the agouti mice--a girl with red hair, hyperphagia, extreme obesity, tall stature, severe hyperinsulinemia and hepatic steatosis.
Nov 1, 2022 • 27 tweets • 9 min read
Excited to share our new preprint in which we report an exome-wide association study of smoking behavior in up-to ~750,000 individuals which discovered a beautiful drug target. Please take a seat. It's storytelling time. 🧵
medrxiv.org/content/10.110… Smoking is the poster child of behavioral traits; it's a compelling example of a behavioral trait where GWAS has led to biologically meaningful signals. e.g. CHRNA5/A3/B4 genes in medial habenula that control aversion to nicotine overdosing.
sciencedirect.com/science/articl…
Oct 30, 2022 • 21 tweets • 5 min read
One thing that stood out for me at the #ASHG22 is that now there is more emphasis being given to genetic diversity in the context of ancestry and its impact on human health. 🧵 It is often considered taboo to talk about phenotypic differences across genetic ancestries. While it is true that many of these differences are environmental in origin, there is sometimes a genetic component as well.
Oct 29, 2022 • 24 tweets • 4 min read
Fantastic talk by @kapoormanav on the genetic architecture of South Asian Indian population based on analysis of more than 15,000 exomes from Rajasthan and Maharashtra states of India. #ASHG22
India is one of the most diverse country in the world with 22 official spoken languages, ~3000 castes, 25,000 sub castes and a population size of 1.4 billion. And yet India is one of the most underrepresented countries in the genetic studies.
Oct 25, 2022 • 14 tweets • 3 min read
Danish Saleheen stunned the audience with his story of building the world's largest cohort of human knockouts in Pakistan, which is the world's 5th most populous country with highest level of consanguinity ever known. #ASHG22 #DRIFT22 Image Starting with around 10k individuals sequenced in 2017, now the cohort comprise of around 200k individuals recruited, of which 80,000 were exome sequenced. Goal is to sequence 1 Million.
nature.com/articles/natur…
Oct 25, 2022 • 7 tweets • 2 min read
Fantastic talk by @cdbustamante about an ambitious initiative to set up one of the world's largest diverse biobank with a focus on Latin American populations with a target sample size of 10 Million(!!). Welcome to the biobank of the Americas! #ASHG22
bbofa.org The motivation behind this massive undertaking is something that is obvious to the field: massive underrepresentation of Non-European populations in the genetic databases.
Oct 9, 2022 • 11 tweets • 3 min read
Stumbled upon this wonderful article today, which highlights the value of human genetics in studying drug side effects. A 🧵 for your Sunday read.
ahajournals.org/doi/10.1161/JA… Image Statins, commonly prescribed cholesterol medications, have a clear mechanism of action: they inhibit HMG-CoA reductase enzyme in liver, leading to up-regulation of LDL receptors and reduction in circulating LDL cholesterol.
app.pulsenotes.com/clinical/pharm… Image
Oct 7, 2022 • 18 tweets • 5 min read
Functional study of six de novo missense variants in KCKN3 identified in 9 probands from the DDD cohort highlights the importance of a K+ channel in the pathophysiology of sleep apnea. Amazing discovery 🧵
@ProfKalium @carolinefwright @mehurles
nature.com/articles/s4158… This is a great example and a reminder that our biological understanding of many of the common diseases (in this case, sleep apnea) come from rare monogenic disorders.
Oct 2, 2022 • 25 tweets • 9 min read
Certain GWAS findings, though not striking themselves, often open doors to literature that are fascinating and enlightening. Let's talk about factor 11, a coagulation factor, which is one of the hits in the recent stroke GWAS. 🧵
Gene F11 codes for coagulation factor X1 that participates in the intrinsic pathway of coagulation cascade, a series of enzymatic activation of coagulation proteins that results in the formation of blood clot.
ncbi.nlm.nih.gov/books/NBK48225…
Sep 30, 2022 • 8 tweets • 2 min read
A GWAS of mucin proteins (MUC5AC, MUC5B) concentration in the sputum sample of COPD patients and controls identifies an interesting finding.
biorxiv.org/content/10.110… Image The authors identified a strong cis pQTL, rs140324259, that decreases the MUC5B concentration in the sputum with an effect that is even stronger than the effect of smoking on sputum.
Jun 14, 2022 • 6 tweets • 2 min read
Great paper showing that those in the UK Biobank who carry deleterious variants in genes known to cause developmental disorders have poor cognitive function, poor education and poor quality of life. Very important work. This is similar to this paper where the authors show those in UKB who carry deleterious variants in genes linked to ASD have poor cognitive function.