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...

A new type of post-translational modification (PTM) revealed: histaminylation. 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...

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.

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...

🚨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🧵

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)?

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

The number also changes (dramatically) depending on whether you include #microproteins 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.

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...

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...

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...

A Critical Introduction to Behavioral Genetics: Q&A with Sasha Gusev ( @sashagusevposts.bsky.social ) 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...

This is amazing.

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....

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 :)

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).

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...

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/

Hey there Bluesky! Looking forward to having high signal / noise in my feed once more

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...

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...

An interesting diagnostic application of CRISPR is to activate expression of genes in tissues where they are not normally expressed. This is useful when studying functional consequence of suspect pathogenic variants in genes that are restricted to inaccessible tissues like brain, eyes etc. 1/

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/

Another beautifully-written piece by @doctorveera.bsky.social 'One of the biggest mysteries of human genome... is the biological mechanism through which noncoding variants influence disease-risks and trait variations.' 💯 www.gwasstories.com/p/de-novo-en...

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/

I wrote about bridging ideographic (dynamic systems) theory in psychology and genetic epidemiology when I couldn't sleep. its about trying to bridge scientific worlds, getting ppl to recognise shared goals, and trying to take English ppl to a good bar in Amsterdam and failing (spelling quality: 3am)

New #somatic variants and candidate genes in patients with focal #epilepsy and structural brain lesions 🧠🧬 Impressive study by Dennis Lal and colleagues 👏👏 First step towards precision medicine is precision diagnosis ‼️ www.nature.com/articles/s41...

Post a photo of yourself from a different era (during medical school internship 2009)

One of the biggest mysteries in Alzheimer's disease that is yet to be solved is the pathogenic mechanism of ApoE4 variant (and the protective mechanism of ApoE2). A new study reports that LDL receptor binding affinity in brain cells linearly increase from E2 to E3 to E4 1/

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.

The human genome is littered with pleiotropic variants with conflicting effects on disease traits, for e.g., increase the risk of one disease but protect against another, or is detrimental early in life but beneficial later.

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...

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.

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...

Geographical distribution of myopia prevalence in China in 2014 vs 2019. The increase in prevalence over time and clustering in certain regions align with the increase in socioeconomic status (and also, likely education). Gao et al. Sci Rep 2024 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...

Freshly published in JASN! Read our perspective on #APOL1 kidney risk variants and their implications, based on the recent H3Africa publication in the NEJM @opeyemiolabisi.bsky.social @gbadegesinlab.bsky.social journals.lww.com/jasn/citatio... www-nejm-org.ezproxy.cul.columbia.edu/doi/10.1056/...

One of the strongest risk loci for SLE lies on the MHC region. Earlier work by Steve McCarroll's group used African ancestry samples to break down the LD between HLA and Complement gene variants and showed that the risk locus is primarily driven by C4 copy number. 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...

Wow, so many new followers!! It's time to resume posting in BlueSky :)

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🧵

Beats closest gene! @jengreitz.bsky.social @anshulkundaje.bsky.social And others that I can't find on bluesky. But if you're here let me know so I can follow you!

I'm here now! Excited to share our latest research published in @Nature 🎉 Huge thanks to my amazing supervisor @hilsomartin and co-first @EmilieWigdor for their incredible support!

A new Substack post on a recent paper in Science Advances that reports interesting GxG interactions for the East-Asian specific ALDH2 variant rs671. www.gwasstories.com/p/a-gene-x-g...