rs11636952 - LMAN1L

Magnitude 2.2 · 8 studies on file

Reported associations

• Sex-specific genetic architecture of blood pressure. - Nature medicine (2024) · Yang ML, Xu C, Gupte T, Hoffmann TJ, Iribarren C, Zhou X, Ganesh SK · PubMed 38459180

  The genetic and genomic basis of sex differences in blood pressure (BP) traits remain unstudied at scale. Here, we conducted sex-stratified and combined-sex genome-wide association studies of BP traits using the UK Biobank resource, identifying 1,346 previously reported and 29 new BP trait-associated loci. Among associated loci, 412 were female-specific (P ≤ 5 × 10 ; P > 5 × 10 ) and 142 were male-specific (P ≤ 5 × 10 ; P > 5 × 10 ); these sex-specific loci were enriched for hormone-related transcription factors, in particular, estrogen receptor 1. Analyses of gene-by-sex interactions and sexually dimorphic effects identified four genomic regions, showing female-specific associations with diastolic BP or pulse pressure, including the chromosome 13q34-COL4A1/

• Leveraging Polygenic Functional Enrichment to Improve GWAS Power. - American journal of human genetics (2019) · Kichaev G, Bhatia G, Loh PR, Gazal S, Burch K, Freund MK, Schoech A, Pasaniuc B, Price AL · PubMed 30595370

  Functional genomics data has the potential to increase GWAS power by identifying SNPs that have a higher prior probability of association. Here, we introduce a method that leverages polygenic functional enrichment to incorporate coding, conserved, regulatory, and LD-related genomic annotations into association analyses. We show via simulations with real genotypes that the method, functionally informed novel discovery of risk loci (FINDOR), correctly controls the false-positive rate at null loci and attains a 9%-38% increase in the number of independent associations detected at causal loci, depending on trait polygenicity and sample size. We applied FINDOR to 27 independent complex traits and diseases from the interim UK Biobank release (average N = 130K). Averaged across traits, we attaine

• A scalable variational inference approach for increased mixed-model association power - Unknown journal (n.d.) · Unknown authors · PubMed 39789286

  ABSTRACT: The rapid growth of modern biobanks is creating new opportunities for large-scale genome-wide association studies (GWASs) and the analysis of complex traits. However, performing GWASs on millions of samples often leads to trade-offs between computational efficiency and statistical power, reducing the benefits of large-scale data collection efforts. We developed Quickdraws, a method that increases association power in quantitative and binary traits without sacrificing computational efficiency, leveraging a spike-and-slab prior on variant effects, stochastic variational inference and graphics processing unit acceleration. We applied Quickdraws to 79 quantitative and 50 binary traits in 405,088 UK Biobank samples, identifying 4.97% and 3.25% more associations than REGENIE and 22.71%

• A Genomics England haplotype reference panel and imputation of UK Biobank - Unknown journal (n.d.) · Unknown authors · PubMed 39134668

  ABSTRACT: We built a reference panel with 342 million autosomal variants using 78,195 individuals from the Genomics England (GEL) dataset, achieving a phasing switch error rate of 0.18% for European samples and imputation quality of r2 = 0.75 for variants with minor allele frequencies as low as 2 × 10−4 in white British samples. The GEL-imputed UK Biobank genome-wide association analysis identified 70% of associations found by direct exome sequencing (P < 2.18 × 10−11), while extending testing of rare variants to the entire genome. Coding variants dominated the rare-variant genome-wide association results, implying less disruptive effects of rare non-coding variants. A Genomics England haplotype reference panel constructed using sequence data from 78,195 individuals

• Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits - Unknown journal (n.d.) · Unknown authors · PubMed 38689001

  ABSTRACT: Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10−8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10−126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10−44) in an independent dataset. Adding PRS into hypertension-pre

• High Blood Pressure and Intraocular Pressure: A Mendelian Randomization Study - Unknown journal (n.d.) · Unknown authors · PubMed 35762941

  ABSTRACT: Purpose To test for causality with regard to the association between blood pressure (BP) and intraocular pressure (IOP) and glaucoma. Methods Single nucleotide polymorphisms (SNPs) associated with BP were identified in a genome-wide association study (GWAS) meta-analysis of 526,001 participants of European ancestry. These SNPs were used to assess the BP versus IOP relationship in a distinct sample (n = 70,832) whose corneal-compensated IOP (IOPcc) was measured. To evaluate the BP versus primary open-angle glaucoma (POAG) relationship, additional Mendelian randomization (MR) analyses were conducted using published GWAS summary statistics. Results Observational analysis revealed a linear relationship between BP traits and IOPcc, with a +0.28 mm Hg increase in IOPcc per 10-mm Hg inc

• Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries - Unknown journal (n.d.) · Unknown authors · PubMed 29912962

  ABSTRACT: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10−5). In Stage 2, these SNVs were tested for inde

• Co-regulatory networks of human serum proteins link genetics to disease - Unknown journal (n.d.) · Unknown authors · PubMed 30072576

  ABSTRACT: Proteins circulating in the blood are critical for age-related disease processes; however, the serum proteome has remained largely unexplored. To this end, 4137 proteins covering most predicted extracellular proteins were measured in the serum of 5457 Icelanders over 65 years of age. Pairwise correlation between proteins as they varied across individuals revealed 27 different network modules of serum proteins, many of which were associated with cardiovascular and metabolic disease states, as well as overall survival. The protein modules were controlled by cis- and trans-acting genetic variants, which in many cases were also associated with complex disease. This revealed co-regulated groups of circulating proteins that incorporated regulatory control between tissues and demonstrat

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