Veera Rajagopal
@doctorveera.bsky.social
MBBS, MD, PhD | GWAS storyteller | Scientist at Regeneron | Human genetics & drug discovery in Neuroscience & Psychiatry
Profiling tandem repeats variations in the population using 1027 long read genomes from All of Us cohort. All the samples are from individuals of African and African American ancestries. 1/
Danxi, Xu et al. bioRxiv
www.biorxiv.org/content/10.1...
Danxi, Xu et al. bioRxiv
www.biorxiv.org/content/10.1...
Detailed tandem repeat allele profiling in 1,027 long-read genomes reveals genome-wide patterns of pathogenicity
Tandem repeats are a highly polymorphic class of genomic variation that play causal roles in rare diseases but are notoriously difficult to sequence using short-read techniques. Most previous studies ...
www.biorxiv.org
January 9, 2025 at 4:37 PM
Profiling tandem repeats variations in the population using 1027 long read genomes from All of Us cohort. All the samples are from individuals of African and African American ancestries. 1/
Danxi, Xu et al. bioRxiv
www.biorxiv.org/content/10.1...
Danxi, Xu et al. bioRxiv
www.biorxiv.org/content/10.1...
A new type of post-translational modification (PTM) revealed: histaminylation.
Zheng, Weekley, Vinson, Zhao, Bastle, et al. Nature
www.nature.com/articles/s41...
Zheng, Weekley, Vinson, Zhao, Bastle, et al. Nature
www.nature.com/articles/s41...
Bidirectional histone monoaminylation dynamics regulate neural rhythmicity - Nature
TG2 functions as an eraser and exchanger of H3 monoaminylations, including histaminylation of Gln5 of histone H3.
www.nature.com
January 9, 2025 at 3:06 PM
A new type of post-translational modification (PTM) revealed: histaminylation.
Zheng, Weekley, Vinson, Zhao, Bastle, et al. Nature
www.nature.com/articles/s41...
Zheng, Weekley, Vinson, Zhao, Bastle, et al. Nature
www.nature.com/articles/s41...
A homozygous SVA retrotransposon insertion is discovered to be likely the most common mutation in ASPA (encodes aspartoacylase) underlying Canavan disease. 1/
Gonzalez, Bell, et al. medRxiv
www.medrxiv.org/content/10.1...
Gonzalez, Bell, et al. medRxiv
www.medrxiv.org/content/10.1...
A Diagnostic Blind Spot: Deep intronic SVA_E Insertion identified as the most Common Pathogenic Variant Associated with Canavan Disease
Canavan disease (CD) is a neurodegenerative disorder caused by biallelic disease-causing variants in the ASPA gene. Here, we utilized long-read sequencing (LRS) to investigate eight individuals clinic...
www.medrxiv.org
December 23, 2024 at 4:59 AM
A homozygous SVA retrotransposon insertion is discovered to be likely the most common mutation in ASPA (encodes aspartoacylase) underlying Canavan disease. 1/
Gonzalez, Bell, et al. medRxiv
www.medrxiv.org/content/10.1...
Gonzalez, Bell, et al. medRxiv
www.medrxiv.org/content/10.1...
Reposted by Veera Rajagopal
Can't comment on the genetics but agree this is a huge "so what?" for clinical practice – we already use patient-specific trends for diagnosis and management and have for decades. The specific examples given in the article (like HCT and CKD) are... amusingly obvious.
December 17, 2024 at 3:10 PM
Can't comment on the genetics but agree this is a huge "so what?" for clinical practice – we already use patient-specific trends for diagnosis and management and have for decades. The specific examples given in the article (like HCT and CKD) are... amusingly obvious.
Reposted by Veera Rajagopal
Arguably the reason that GWAS for blood traits have ever worked is that we are proxying the individual set point. So yes the clinical discussion is neat. The genetic implications seem nil.
December 17, 2024 at 3:03 PM
Arguably the reason that GWAS for blood traits have ever worked is that we are proxying the individual set point. So yes the clinical discussion is neat. The genetic implications seem nil.
Controversial take: this is interesting, but still I am failing to see what is groundbreaking about it as many are praising it to be. 1/
Foy et al. Nature
www.nature.com/articles/s41...
Foy et al. Nature
www.nature.com/articles/s41...
Haematological setpoints are a stable and patient-specific deep phenotype - Nature
Complete blood count indices are tightly regulated around setpoints for decades in healthy adults, and represent a deep phenotype providing opportunities for investigating differential disease risks, ...
www.nature.com
December 17, 2024 at 5:44 AM
Controversial take: this is interesting, but still I am failing to see what is groundbreaking about it as many are praising it to be. 1/
Foy et al. Nature
www.nature.com/articles/s41...
Foy et al. Nature
www.nature.com/articles/s41...
Reposted by Veera Rajagopal
🚨New preprint out❗️
Using human genetic data we explored IL-6 signaling as a potential target for cerebral small vessel disease (cSVD)🧬🧠
We found no convincing associations between genetically downregulated IL-6 signaling and
👉clinical outcomes
👉MRI markers
👉pathology hallmarks
of cSVD🧵
Using human genetic data we explored IL-6 signaling as a potential target for cerebral small vessel disease (cSVD)🧬🧠
We found no convincing associations between genetically downregulated IL-6 signaling and
👉clinical outcomes
👉MRI markers
👉pathology hallmarks
of cSVD🧵
December 15, 2024 at 9:44 PM
🚨New preprint out❗️
Using human genetic data we explored IL-6 signaling as a potential target for cerebral small vessel disease (cSVD)🧬🧠
We found no convincing associations between genetically downregulated IL-6 signaling and
👉clinical outcomes
👉MRI markers
👉pathology hallmarks
of cSVD🧵
Using human genetic data we explored IL-6 signaling as a potential target for cerebral small vessel disease (cSVD)🧬🧠
We found no convincing associations between genetically downregulated IL-6 signaling and
👉clinical outcomes
👉MRI markers
👉pathology hallmarks
of cSVD🧵
Reposted by Veera Rajagopal
The truth is nobody should care how many protein coding genes there are. The gene is a useful abstraction that loses its utility when defined precisely enough to count.
Exactly how many protein-coding genes are there in the human genome? The truth is no one knows. The numbers change based on what database you use as reference.
December 15, 2024 at 3:46 PM
The truth is nobody should care how many protein coding genes there are. The gene is a useful abstraction that loses its utility when defined precisely enough to count.
Does it make sense to still use P<5e-8 as significance threshold in today's GWASs that include more and more rare variants (as the imputation quality continuously improve with large data and better reference panels)?
December 15, 2024 at 1:37 PM
Does it make sense to still use P<5e-8 as significance threshold in today's GWASs that include more and more rare variants (as the imputation quality continuously improve with large data and better reference panels)?
Reposted by Veera Rajagopal
Challenging when annotating variants, especially for discovery studies. And when looking at different transcripts for each gene, the numbers and sequences change wildly across databases. Many transcripts share only the gene name and not the function: the question mark on encoded proteins is huge
Exactly how many protein-coding genes are there in the human genome? The truth is no one knows. The numbers change based on what database you use as reference.
December 15, 2024 at 1:35 PM
Challenging when annotating variants, especially for discovery studies. And when looking at different transcripts for each gene, the numbers and sequences change wildly across databases. Many transcripts share only the gene name and not the function: the question mark on encoded proteins is huge
Reposted by Veera Rajagopal
The number also changes (dramatically) depending on whether you include #microproteins
Cc: @thomasmartinez.bsky.social
Cc: @thomasmartinez.bsky.social
Exactly how many protein-coding genes are there in the human genome? The truth is no one knows. The numbers change based on what database you use as reference.
December 15, 2024 at 1:30 PM
The number also changes (dramatically) depending on whether you include #microproteins
Cc: @thomasmartinez.bsky.social
Cc: @thomasmartinez.bsky.social
Exactly how many protein-coding genes are there in the human genome? The truth is no one knows. The numbers change based on what database you use as reference.
December 15, 2024 at 1:11 PM
Exactly how many protein-coding genes are there in the human genome? The truth is no one knows. The numbers change based on what database you use as reference.
Reposted by Veera Rajagopal
It's nice to see that we pick up this intron retention variant in the eQTL Catalogue as well. Smallest p-value in BrainSeq, but also detected in multiple GTEx tissues and other studies that contain African genetic ancestry individuals (e.g. Quach 2016 monocytes).
elixir.ut.ee/eqtl/?credib...
elixir.ut.ee/eqtl/?credib...
December 15, 2024 at 7:31 AM
It's nice to see that we pick up this intron retention variant in the eQTL Catalogue as well. Smallest p-value in BrainSeq, but also detected in multiple GTEx tissues and other studies that contain African genetic ancestry individuals (e.g. Quach 2016 monocytes).
elixir.ut.ee/eqtl/?credib...
elixir.ut.ee/eqtl/?credib...
Dissecting the mechanism of African ancestries-enriched GBA1 risk variant for Parkinson's disease (PD). A cool example to remind we shouldn't always expect 1-1 relationship between RNA and protein expression. 1/
Álvarez Jerez, Wild Crea, et al. Nat Struct Mol Bio
www.nature.com/articles/s41...
Álvarez Jerez, Wild Crea, et al. Nat Struct Mol Bio
www.nature.com/articles/s41...
December 15, 2024 at 5:30 AM
Dissecting the mechanism of African ancestries-enriched GBA1 risk variant for Parkinson's disease (PD). A cool example to remind we shouldn't always expect 1-1 relationship between RNA and protein expression. 1/
Álvarez Jerez, Wild Crea, et al. Nat Struct Mol Bio
www.nature.com/articles/s41...
Álvarez Jerez, Wild Crea, et al. Nat Struct Mol Bio
www.nature.com/articles/s41...
Reposted by Veera Rajagopal
Fascinating paper on individual setpoints for blood count variables. Much better risk estimation when you interpret any given measurement from a person in light of all previous measurements. And I bet it is applicable much more widely to other blood tests. www.nature.com/articles/s41...
Haematological setpoints are a stable and patient-specific deep phenotype - Nature
Complete blood count indices are tightly regulated around setpoints for decades in healthy adults, and represent a deep phenotype providing opportunities for investigating differential disease risks, ...
www.nature.com
December 14, 2024 at 3:10 PM
Fascinating paper on individual setpoints for blood count variables. Much better risk estimation when you interpret any given measurement from a person in light of all previous measurements. And I bet it is applicable much more widely to other blood tests. www.nature.com/articles/s41...
Reposted by Veera Rajagopal
A Critical Introduction to Behavioral Genetics: Q&A with Sasha Gusev ( @sashagusevposts.bsky.social )
www.psychiatrymargins.com/p/a-critical...
www.psychiatrymargins.com/p/a-critical...
A Critical Introduction to Behavioral Genetics: Q&A with Sasha Gusev
Sasha Gusev is a statistical geneticist and an Associate Professor of Medicine at Harvard Medical School and the Dana-Farber Cancer Institute.
www.psychiatrymargins.com
December 14, 2024 at 2:19 PM
A Critical Introduction to Behavioral Genetics: Q&A with Sasha Gusev ( @sashagusevposts.bsky.social )
www.psychiatrymargins.com/p/a-critical...
www.psychiatrymargins.com/p/a-critical...
mRNA therapy for preeclampsia:
Lipid nanoparticles-based delivery of VEGF mRNA to placenta (functional VEGF deficiency plays role in preeclampsia) restores endothelial dysfunction in a mouse model of preeclampsia.
News and Views in Nature by Thadhani & Karumanchi
www.nature.com/articles/d41...
Lipid nanoparticles-based delivery of VEGF mRNA to placenta (functional VEGF deficiency plays role in preeclampsia) restores endothelial dysfunction in a mouse model of preeclampsia.
News and Views in Nature by Thadhani & Karumanchi
www.nature.com/articles/d41...
December 13, 2024 at 3:55 AM
mRNA therapy for preeclampsia:
Lipid nanoparticles-based delivery of VEGF mRNA to placenta (functional VEGF deficiency plays role in preeclampsia) restores endothelial dysfunction in a mouse model of preeclampsia.
News and Views in Nature by Thadhani & Karumanchi
www.nature.com/articles/d41...
Lipid nanoparticles-based delivery of VEGF mRNA to placenta (functional VEGF deficiency plays role in preeclampsia) restores endothelial dysfunction in a mouse model of preeclampsia.
News and Views in Nature by Thadhani & Karumanchi
www.nature.com/articles/d41...
Reposted by Veera Rajagopal
This is amazing.
Association of polygenic scores for neuropsychiatric traits with self-reported professions based on analysis of 420k individuals from UK Biobank and Million Veteran Program. Look at the 'arts & design' category. Artistic talent comes at a cost--a piece of your mind :)
December 12, 2024 at 9:31 AM
This is amazing.
Reposted by Veera Rajagopal
Reminds me of an old deCODE paper! Though I'm not sure I would endorse the causal langauge used here. www.nature.com/articles/nn....
Polygenic risk scores for schizophrenia and bipolar disorder predict creativity - Nature Neuroscience
Genetic risk scores derived from GWAS of psychotic disorders are greater in creative professionals unaffected by psychosis. This association cannot be explained by shared environment or education. Thu...
www.nature.com
December 12, 2024 at 10:56 AM
Reminds me of an old deCODE paper! Though I'm not sure I would endorse the causal langauge used here. www.nature.com/articles/nn....
Reposted by Veera Rajagopal
This is one of the most interesting plots I’ve seen in ages. Just look at the professional dendrogram that results from clustering in this way!
Association of polygenic scores for neuropsychiatric traits with self-reported professions based on analysis of 420k individuals from UK Biobank and Million Veteran Program. Look at the 'arts & design' category. Artistic talent comes at a cost--a piece of your mind :)
December 12, 2024 at 7:48 AM
This is one of the most interesting plots I’ve seen in ages. Just look at the professional dendrogram that results from clustering in this way!
Association of polygenic scores for neuropsychiatric traits with self-reported professions based on analysis of 420k individuals from UK Biobank and Million Veteran Program. Look at the 'arts & design' category. Artistic talent comes at a cost--a piece of your mind :)
December 12, 2024 at 6:14 AM
Association of polygenic scores for neuropsychiatric traits with self-reported professions based on analysis of 420k individuals from UK Biobank and Million Veteran Program. Look at the 'arts & design' category. Artistic talent comes at a cost--a piece of your mind :)
Reposted by Veera Rajagopal
This is an interesting one...
www.nejm.org/image-challe...
Some thoughts in my reply, with spoilers about what condition this is (though I don't name it).
www.nejm.org/image-challe...
Some thoughts in my reply, with spoilers about what condition this is (though I don't name it).
December 5, 2024 | NEJM
Image Challenge from the New England Journal of Medicine — December 5, 2024
www.nejm.org
December 8, 2024 at 4:39 PM
This is an interesting one...
www.nejm.org/image-challe...
Some thoughts in my reply, with spoilers about what condition this is (though I don't name it).
www.nejm.org/image-challe...
Some thoughts in my reply, with spoilers about what condition this is (though I don't name it).
This is a fascinating preprint. A spontaneously occurring feline model of atherosclerosis caused by a homozygous loss of function mutation in LDLR. 1/
Hytönen et al. bioRxiv
www.biorxiv.org/content/10.1...
Hytönen et al. bioRxiv
www.biorxiv.org/content/10.1...
A feline model of human LDLR-related atherosclerosis
Background: Atherosclerosis, a chronic inflammatory vascular disease driven by the accumulation of LDL-derived cholesterol on arterial walls, is the leading cause of mortality worldwide but is rare in...
www.biorxiv.org
December 8, 2024 at 4:51 PM
This is a fascinating preprint. A spontaneously occurring feline model of atherosclerosis caused by a homozygous loss of function mutation in LDLR. 1/
Hytönen et al. bioRxiv
www.biorxiv.org/content/10.1...
Hytönen et al. bioRxiv
www.biorxiv.org/content/10.1...
I've always wondered about the pigmentation GWAS signals like TYR, OCA2 etc. in the GWAS of OCT-derived phenotypes. A new preprint elegantly investigates the phenotypic and genetic correlation between retinal pigment epithelium (RPE) thickness (which is measured using OCT) 1/
December 8, 2024 at 4:17 AM
I've always wondered about the pigmentation GWAS signals like TYR, OCA2 etc. in the GWAS of OCT-derived phenotypes. A new preprint elegantly investigates the phenotypic and genetic correlation between retinal pigment epithelium (RPE) thickness (which is measured using OCT) 1/
Reposted by Veera Rajagopal
Hey there Bluesky! Looking forward to having high signal / noise in my feed once more
December 6, 2024 at 2:14 PM
Hey there Bluesky! Looking forward to having high signal / noise in my feed once more