rs12340775 - MPDZ

Magnitude 2.0 · 8 studies on file

Reported associations

• Genome-wide Associations Reveal Human-Mouse Genetic Convergence and Modifiers of Myogenesis, CPNE1 and STC2. - American journal of human genetics (2020) · Hernandez Cordero AI, Gonzales NM, Parker CC, Sokolof G, Vandenbergh DJ, Cheng R, Abney M, Sko A, Douglas A, Palmer AA, Gregory JS, Lionikas A · PubMed 31761296

  Muscle bulk in adult healthy humans is highly variable even after height, age, and sex are accounted for. Low muscle mass, due to fewer and/or smaller constituent muscle fibers, would exacerbate the impact of muscle loss occurring in aging or disease. Genetic variability substantially influences muscle mass differences, but causative genes remain largely unknown. In a genome-wide association study (GWAS) on appendicular lean mass (ALM) in a population of 85,750 middle-aged (aged 38-49 years) individuals from the UK Biobank (UKB), we found 182 loci associated with ALM (p < 5 × 10 ). We replicated associations for 78% of these loci (p < 5 × 10 ) with ALM in a population of 181,862 elderly (aged 60-74 years) individuals from UKB. We also conducted a GWAS on hindlimb skeletal muscle m

• 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

• Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis - Unknown journal (n.d.) · Unknown authors · PubMed 28869591

  ABSTRACT: Osteoporosis is a common disease diagnosed primarily by measurement of bone mineral density (BMD). We undertook a genome-wide association study in 142,487 individuals from the UK Biobank to identify loci associated with BMD estimated by quantitative ultrasound of the heel ("eBMD"). We identified 307 conditionally independent SNPs attaining genome-wide significance at 203 loci, explaining approximately 12% of the phenotypic variance. These included 153 novel loci, and several rare variants with large effect sizes. To investigate underlying mechanisms we undertook: 1) bioinformatic, functional genomic annotation and human osteoblast expression studies; 2) gene function prediction; 3) skeletal phenotyping of 120 knockout mice with deletions of genes adjacent to lead independent

• Dissection of genetic variation and evidence for pleiotropy in male pattern baldness - Unknown journal (n.d.) · Unknown authors · PubMed 30573740

  ABSTRACT: Male pattern baldness (MPB) is a sex-limited, age-related, complex trait. We study MPB genetics in 205,327 European males from the UK Biobank. Here we show that MPB is strongly heritable and polygenic, with pedigree-heritability of 0.62 (SE = 0.03) estimated from close relatives, and SNP-heritability of 0.39 (SE = 0.01) from conventionally-unrelated males. We detect 624 near-independent genome-wide loci, contributing SNP-heritability of 0.25 (SE = 0.01), of which 26 X-chromosome loci explain 11.6%. Autosomal genetic variance is enriched for common variants and regions of lower linkage disequilibrium. We identify plausible genetic correlations between MPB and multiple sex-limited markers of earlier puberty, increased bone mineral density (rg = 0.15) and pancreati

• 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 saturated map of common genetic variants associated with human height - Unknown journal (n.d.) · Unknown authors · PubMed 36224396

  ABSTRACT: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation

• Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry - Unknown journal (n.d.) · Unknown authors · PubMed 30239722

  ABSTRACT: Abstract More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR

• Identification of 613 new loci associated with heel bone mineral density and a polygenic risk score for bone mineral density, osteoporosis and fracture - Unknown journal (n.d.) · Unknown authors · PubMed 30048462

  ABSTRACT: Low bone mineral density (BMD) leads to osteoporosis, and is a risk factor for bone fractures, including stress fractures. Using data from UK Biobank, a genome-wide association study identified 1,362 independent SNPs that clustered into 899 loci of which 613 are new. These data were used to train a genetic algorithm using 22,886 SNPs as predictors and showing a correlation with heel bone mineral density of 0.415. Combining this genetic algorithm with height, weight, age and sex resulted in a correlation with heel bone mineral density of 0.496. Individuals with low scores (2.2% of total) showed a change in BMD of -1.16 T-score units, an increase in risk for osteoporosis of 17.4 fold and an increase in risk for fracture of 1.87 fold. Genetic predictors could assist in the identific

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