Andrew Brown
@arnsbr.bsky.social
Will do statistical genetics for potaje de garbanzos.
Ok, but BMI is a terrible metric to study T2D, and maybe disease subtypes are still something to consider. So we call our friend Dina Mansour Aly, used the summary statistic of her GWAS study in 5 T2D subtypes.
November 13, 2024 at 1:37 PM
Ok, but BMI is a terrible metric to study T2D, and maybe disease subtypes are still something to consider. So we call our friend Dina Mansour Aly, used the summary statistic of her GWAS study in 5 T2D subtypes.
We tested using GWAS summary statistics with BMI control, expecting fewer genes in obesity-related tissues like adipose but increased power in beta cell tissues by reducing variation. But all tissues lost genes, and there was no link with the relevance of the tissue for obesity.
November 13, 2024 at 1:37 PM
We tested using GWAS summary statistics with BMI control, expecting fewer genes in obesity-related tissues like adipose but increased power in beta cell tissues by reducing variation. But all tissues lost genes, and there was no link with the relevance of the tissue for obesity.
So, can we stop collecting “difficult” tissues? NO! Remember that when comparing across tissues, ~50% of the genes only showed one tissue. For example, 𝘛𝘊𝘍7𝘓2 was only found using pancreatic islets, the only tissue reporting an eQTL involving the known T2D-GWAS loci.
November 13, 2024 at 1:37 PM
So, can we stop collecting “difficult” tissues? NO! Remember that when comparing across tissues, ~50% of the genes only showed one tissue. For example, 𝘛𝘊𝘍7𝘓2 was only found using pancreatic islets, the only tissue reporting an eQTL involving the known T2D-GWAS loci.
Could we validate our genes with another approach? We conducted multiple instrument Mendelian Randomization testing to assess concordant SNP effects on both gene expression change and T2D risk, again finding more significant genes in the DIRECT study, supported by more SNPs.
November 13, 2024 at 1:37 PM
Could we validate our genes with another approach? We conducted multiple instrument Mendelian Randomization testing to assess concordant SNP effects on both gene expression change and T2D risk, again finding more significant genes in the DIRECT study, supported by more SNPs.
In total, across all 51 datasets, we found 1,818 genes and 7 proteins relevant for T2D, of which 404 were identified using the whole blood large dataset (DIRECT). GTEx (n<706) identified a total of 1,568, but no tissue found more than 299 genes.
November 13, 2024 at 1:37 PM
In total, across all 51 datasets, we found 1,818 genes and 7 proteins relevant for T2D, of which 404 were identified using the whole blood large dataset (DIRECT). GTEx (n<706) identified a total of 1,568, but no tissue found more than 299 genes.
Comparing relevant vs well powered reference panels, we found that sample size,not tissue relevance for the disease, drove gene discovery in T2D (A). The relationship between sample size and discovery was almost linear (B), with maybe saturation for the largest dataset (n=3,029).
November 13, 2024 at 1:37 PM
Comparing relevant vs well powered reference panels, we found that sample size,not tissue relevance for the disease, drove gene discovery in T2D (A). The relationship between sample size and discovery was almost linear (B), with maybe saturation for the largest dataset (n=3,029).
We discuss the trade-off between sample size and tissue specificity of molecular datasets for the study of T2D, by using TWAS methods on three gene expression reference panels with sample sizes ranging from 70 to 3,029, from 51 human tissues, to find T2D causal genes.
November 13, 2024 at 1:37 PM
We discuss the trade-off between sample size and tissue specificity of molecular datasets for the study of T2D, by using TWAS methods on three gene expression reference panels with sample sizes ranging from 70 to 3,029, from 51 human tissues, to find T2D causal genes.
I am very excited and proud to announce this preprint covering one part of the work done during my PhD! Impact of sample size and tissue relevance on Type 2 Diabetes gene identification. [Thread] www.medrxiv.org/content/10.1...
November 13, 2024 at 1:37 PM
I am very excited and proud to announce this preprint covering one part of the work done during my PhD! Impact of sample size and tissue relevance on Type 2 Diabetes gene identification. [Thread] www.medrxiv.org/content/10.1...