Veera Rajagopal
@doctorveera.bsky.social
MBBS, MD, PhD | GWAS storyteller | Scientist at Regeneron | Human genetics & drug discovery in Neuroscience & Psychiatry
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.
Last year, a GWAS of PD in African ancestries identified a single, strong signal at the well known GBA1 region in chromosome 1. The risk variant was found to be very common in African ancestries but rare in others. 2/
www.thelancet.com/journals/lan...
www.thelancet.com/journals/lan...
December 15, 2024 at 5:30 AM
Last year, a GWAS of PD in African ancestries identified a single, strong signal at the well known GBA1 region in chromosome 1. The risk variant was found to be very common in African ancestries but rare in others. 2/
www.thelancet.com/journals/lan...
www.thelancet.com/journals/lan...
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...
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...
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 :)
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/
Nice visualization of the extensive pleiotropy of multiple sclerosis (MS)-associated GWAS signals with a wide range of autoimmune diseases. 1/
Zeng, Atlas, et al. medRxiv
www.medrxiv.org/content/10.1...
Zeng, Atlas, et al. medRxiv
www.medrxiv.org/content/10.1...
December 6, 2024 at 2:14 PM
Nice visualization of the extensive pleiotropy of multiple sclerosis (MS)-associated GWAS signals with a wide range of autoimmune diseases. 1/
Zeng, Atlas, et al. medRxiv
www.medrxiv.org/content/10.1...
Zeng, Atlas, et al. medRxiv
www.medrxiv.org/content/10.1...
Analysis of sequencing data of 320k individuals (75k cases and 245k controls) shows heterozygous carriers of cystic fibrosis mutations are protected from inflammatory bowel disease.
Yu et al. medRxiv (from International IBD consortium)
www.medrxiv.org/content/10.1...
Yu et al. medRxiv (from International IBD consortium)
www.medrxiv.org/content/10.1...
December 6, 2024 at 9:23 AM
Analysis of sequencing data of 320k individuals (75k cases and 245k controls) shows heterozygous carriers of cystic fibrosis mutations are protected from inflammatory bowel disease.
Yu et al. medRxiv (from International IBD consortium)
www.medrxiv.org/content/10.1...
Yu et al. medRxiv (from International IBD consortium)
www.medrxiv.org/content/10.1...
I learned about this first time in ASHG 2023 (x.com/doctorveera/...) in an abstract from researchers from University of Adelaide who presented on a CRISPR activation technique called "suntag". 4/
December 2, 2024 at 1:29 PM
I learned about this first time in ASHG 2023 (x.com/doctorveera/...) in an abstract from researchers from University of Adelaide who presented on a CRISPR activation technique called "suntag". 4/
I was reading about the genetics of ovarian aging, particularly on the link between breast cancer genes and age at menopause. The below plot is from a 2021 study that looked into rare variant associations with age at natural menopause using exome data of 50k women in the UK Biobank. 1/
December 1, 2024 at 5:06 PM
I was reading about the genetics of ovarian aging, particularly on the link between breast cancer genes and age at menopause. The below plot is from a 2021 study that looked into rare variant associations with age at natural menopause using exome data of 50k women in the UK Biobank. 1/
Life stories of scientists where genetics become more than just a career, a mission to search for answers that explain one's life events, is always utterly fascinating. I enjoyed listening to Prof. Susan Weiss Liebman share her life story in The Genetics Podcast (youtube.com/watch?v=hXlb...) 1/
December 1, 2024 at 2:27 PM
Life stories of scientists where genetics become more than just a career, a mission to search for answers that explain one's life events, is always utterly fascinating. I enjoyed listening to Prof. Susan Weiss Liebman share her life story in The Genetics Podcast (youtube.com/watch?v=hXlb...) 1/
Post a photo of yourself from a different era (during medical school internship 2009)
November 30, 2024 at 4:06 PM
Post a photo of yourself from a different era (during medical school internship 2009)
Great question. Hope someone looks into it. But note that a functional LDLR might be important for neuronal survival as there are other ligands like Aβ might depend on a functional LDLR.
November 30, 2024 at 3:42 PM
Great question. Hope someone looks into it. But note that a functional LDLR might be important for neuronal survival as there are other ligands like Aβ might depend on a functional LDLR.
Making a case for GLP1 agonists use for alcohol use disorder (AUD) using Swedish registry data. During an 8-year follow-up, individuals with AUD who were also on treatment with GLP1 agonists (for obesity or T2D) were hospitalized less frequently for AUD-related reasons.
November 30, 2024 at 9:05 AM
Making a case for GLP1 agonists use for alcohol use disorder (AUD) using Swedish registry data. During an 8-year follow-up, individuals with AUD who were also on treatment with GLP1 agonists (for obesity or T2D) were hospitalized less frequently for AUD-related reasons.
Heterozygous mutations in leptin receptor gene (LEPR) do not cause obesity. The finding goes against the rationale for a recent clinical trial that test setmelanotide for obesity treatment in heterozygous carriers of LEPR variants.
Delplanque et al. AJHG
www.sciencedirect.com/science/arti...
Delplanque et al. AJHG
www.sciencedirect.com/science/arti...
November 29, 2024 at 2:20 AM
Heterozygous mutations in leptin receptor gene (LEPR) do not cause obesity. The finding goes against the rationale for a recent clinical trial that test setmelanotide for obesity treatment in heterozygous carriers of LEPR variants.
Delplanque et al. AJHG
www.sciencedirect.com/science/arti...
Delplanque et al. AJHG
www.sciencedirect.com/science/arti...
One of the underrated uses of plasma proteins is disease prediction. They predict most disease conditions surprisingly well, even better than demographics model. The plot compares AUC of plasma protein risk scores vs demographics in predicting disease endpoints in the UK Biobank.
November 28, 2024 at 5:24 PM
One of the underrated uses of plasma proteins is disease prediction. They predict most disease conditions surprisingly well, even better than demographics model. The plot compares AUC of plasma protein risk scores vs demographics in predicting disease endpoints in the UK Biobank.
Another beautiful human genetics work from Po-Ru Loh, Steve McCarroll and team. Work led by incredibly talented Margaux Louise Anna Hujoel.
x.com/HujoelM/stat...
x.com/HujoelM/stat...
November 28, 2024 at 1:45 PM
Another beautiful human genetics work from Po-Ru Loh, Steve McCarroll and team. Work led by incredibly talented Margaux Louise Anna Hujoel.
x.com/HujoelM/stat...
x.com/HujoelM/stat...
Striking similarity of some of the genetic signals in mismatch repair genes (MSH3, FAN1 and PMS2) between GWAS of somatic expansion of CAG repeats in TCF4 gene (estimated from UKB WGS data) & GWAS of age at onset of cognitive changes in Huntington's.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
November 28, 2024 at 1:43 PM
Striking similarity of some of the genetic signals in mismatch repair genes (MSH3, FAN1 and PMS2) between GWAS of somatic expansion of CAG repeats in TCF4 gene (estimated from UKB WGS data) & GWAS of age at onset of cognitive changes in Huntington's.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Education causally relates to myopia risk, a classic application for Mendelian Randomization. Fascinatingly, the relationship is complex with better visual acuity increasing school performance in children and increased education increasing myopia risk in adults.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
November 28, 2024 at 7:55 AM
Education causally relates to myopia risk, a classic application for Mendelian Randomization. Fascinatingly, the relationship is complex with better visual acuity increasing school performance in children and increased education increasing myopia risk in adults.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Timeline of advances in mouse genetics
"Twenty-first century mouse genetics is again at an inflection point" Fang & Peltz, Lab Anim 2024
www.nature.com/articles/s41...
"Twenty-first century mouse genetics is again at an inflection point" Fang & Peltz, Lab Anim 2024
www.nature.com/articles/s41...
November 28, 2024 at 7:51 AM
Timeline of advances in mouse genetics
"Twenty-first century mouse genetics is again at an inflection point" Fang & Peltz, Lab Anim 2024
www.nature.com/articles/s41...
"Twenty-first century mouse genetics is again at an inflection point" Fang & Peltz, Lab Anim 2024
www.nature.com/articles/s41...
Comparison of pathway-specific polygenic risk score for type 2 diabetes between Europeans (purple) vs South Asians (green; Pakistanis & Bangladeshis).
Hodgson et al. Nat Med
www.nature.com/articles/s41...
Hodgson et al. Nat Med
www.nature.com/articles/s41...
November 27, 2024 at 3:24 PM
Comparison of pathway-specific polygenic risk score for type 2 diabetes between Europeans (purple) vs South Asians (green; Pakistanis & Bangladeshis).
Hodgson et al. Nat Med
www.nature.com/articles/s41...
Hodgson et al. Nat Med
www.nature.com/articles/s41...
January 9, 2024 at 4:18 AM
GWAS and ExWAS of human hypothalamus volumes identify a strong association with ADAMTS8 (encodes an angiogenesis-inhibiting enzyme), implicated by common variants, rare variants, and eQTLs. Fascinating!
Chen, You, Zhang, Wu, et al. Nat Hum Behav
Chen, You, Zhang, Wu, et al. Nat Hum Behav
January 6, 2024 at 2:36 PM
GWAS and ExWAS of human hypothalamus volumes identify a strong association with ADAMTS8 (encodes an angiogenesis-inhibiting enzyme), implicated by common variants, rare variants, and eQTLs. Fascinating!
Chen, You, Zhang, Wu, et al. Nat Hum Behav
Chen, You, Zhang, Wu, et al. Nat Hum Behav
Rare variant associations with sleep-related traits in the UK Biobank
Fei, Li, Ning, Yang, et al. Nat Hum Behav
www.nature.com/articles/s41...
Fei, Li, Ning, Yang, et al. Nat Hum Behav
www.nature.com/articles/s41...
January 6, 2024 at 2:35 PM
Rare variant associations with sleep-related traits in the UK Biobank
Fei, Li, Ning, Yang, et al. Nat Hum Behav
www.nature.com/articles/s41...
Fei, Li, Ning, Yang, et al. Nat Hum Behav
www.nature.com/articles/s41...
Major depression is understandably one of the most difficult phenotypes to define, which makes it challenging to replicate genetic findings even across samples within an ancestry, let alone across ancestries.
Meng, Navoly, Giannakopoulou, et al. Nat Gen
www.nature.com/articles/s41...
Meng, Navoly, Giannakopoulou, et al. Nat Gen
www.nature.com/articles/s41...
January 6, 2024 at 2:34 PM
Major depression is understandably one of the most difficult phenotypes to define, which makes it challenging to replicate genetic findings even across samples within an ancestry, let alone across ancestries.
Meng, Navoly, Giannakopoulou, et al. Nat Gen
www.nature.com/articles/s41...
Meng, Navoly, Giannakopoulou, et al. Nat Gen
www.nature.com/articles/s41...