Ask about this productRelated genes to: PHTF1 antibody
- Gene:
- PHTF1 NIH gene
- Name:
- putative homeodomain transcription factor 1
- Previous symbol:
- PHTF
- Synonyms:
- -
- Chromosome:
- 1p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-03-24
- Date modifiied:
- 2015-02-16
Related products to: PHTF1 antibody
Related articles to: PHTF1 antibody
- While disease-associated variants identified by genome-wide association studies (GWAS) most likely regulate gene expression levels, linking variants to target genes is critical to determining the functional mechanisms of these variants. Genetic effects on gene expression have been extensively characterized by expression quantitative trait loci (eQTL) studies, yet data from non-European populations is limited. This restricts our understanding of disease to genes whose regulatory variants are common in European populations. While previous work has leveraged data from multiple populations to improve GWAS power and polygenic risk score (PRS) accuracy, multi-ancestry data has not yet been used to better estimate -genetic effects on gene expression. Here, we present a new method, Multi-Ancestry Gene Expression Prediction Regularized Optimization (MAGEPRO), which constructs robust genetic models of gene expression in understudied populations or cell types by fitting a regularized linear combination of eQTL summary data across diverse cohorts. In simulations, our tool generates more accurate models of gene expression than widely-used LASSO and the state-of-the-art multi-ancestry PRS method, PRS-CSx, adapted to gene expression prediction. We attribute this improvement to MAGEPRO's ability to more accurately estimate causal eQTL effect sizes ( < 3.98 × 10, two-sided paired t-test). With real data, we applied MAGEPRO to 8 eQTL cohorts representing 3 ancestries (average = 355) and consistently outperformed each of 6 competing methods in gene expression prediction tasks. Integration with GWAS summary statistics across 66 complex traits (representing 22 phenotypes and 3 ancestries) resulted in 2,331 new gene-trait associations, many of which replicate across multiple ancestries, including linked to white blood cell count, a gene which is overexpressed in leukemia patients. MAGEPRO also identified biologically plausible novel findings, such as an essential component of GPI biosynthesis, associated with heart failure, which has been previously evidenced by clinical outcome data. Overall, MAGEPRO is a powerful tool to enhance inference of gene regulatory effects in underpowered datasets and has improved our understanding of population-specific and shared genetic effects on complex traits. - Source: PubMed
Publication date: 2024/09/26
Akamatsu KaiGolzari StephenAmariuta Tiffany - A genome-wide association study (GWAS) in Caucasian population identified five non-MHC genes (, and ) associated with risk of the co-occurrence of autoimmune thyroid diseases (AITD) and type 1 diabetes (T1D). The aim of this study is to replicate these associations with AITD in patients with T1D in Chinese Han population. - Source: PubMed
Publication date: 2021/07/01
Liang JialinLiang GanxiongLiu ZhonghuaCai Huan - Genome-wide association studies (GWASs) have identified hundreds of genetic loci for osteoporosis (OP) and rheumatoid arthritis (RA), individually, however, a large proportion of the total trait heritability remains unexplained. Previous studies demonstrated that these two diseases may share some common genetic determination and risk factors, but they were generally focused on individual trait and failed to identify the common variants that play key functional roles in the etiology of these two diseases. Here, we performed a conditional false discovery rate (cFDR) analysis to identify novel pleiotropic variants shared between them by integrating two independent GWASs with summary statistics for total body bone mineral density (TB-BMD, a major risk factor for osteoporosis) (n = 66,628) and RA (n = 58,284). A fine-mapping approach was also applied to identify the most probable causal variants with biological effects on both TB-BMD and RA. As a result, we found 47 independent pleiotropic SNPs shared between TB-BMD and RA, and 40 of them were validated in heel ultrasound estimated BMD (eBMD), femoral neck BMD (FN-BMD) or lumbar spine (LS-BMD). We detected one SNP (rs13299616) was novel and not identified by previous BMD or RA-related studies. Combined with fine-mapping and GWAS-eQTL colocalization analyses, our results suggested that locus 1p13.2 (including PTPN22, MAGI3, PHTF1, and RSBN1) was an important region to regulate TB-BMD and RA simultaneously. These findings provide new insights into the shared biological mechanisms and functional genetic determinants between OP and RA, and novel potential targets for treatment development. - Source: PubMed
Publication date: 2021/03/19
Liu Ying-QiLiu YongZhang QiangXiao TaoDeng Hong-Wen - Cardiomyopathy occurs at significantly higher rates in survivors of childhood cancer than the general population, but few studies have evaluated racial or ethnic disparities, and none have assessed potential genetic factors contributing to this outcome. In this study, childhood cancer survivors of African ancestry exposed to cardiotoxic therapies (anthracyclines and/or heart radiotherapy; = 246) were compared with cardiotoxic-exposed survivors of European ancestry ( = 1,645) in the St. Jude Lifetime Cohort. Genetic variants were examined using whole-genome sequencing data among survivors of African ancestry, first based on ejection fraction (EF) as a continuous outcome, followed by clinical history of cardiomyopathy. Survivors of African ancestry showed 1.53- and 2.47-fold risks of CTCAE grade 2-4 and grade 3-4 cardiomyopathy than survivors of European ancestry. A novel locus at 1p13.2 showed significant association with EF (rs6689879*C: EF reduction = 4.2%; = 2.8 × 10) in 246 survivors of African ancestry, which was successfully replicated in 1,645 survivors of European ancestry but with attenuated magnitude (EF reduction = 0.4%; = 0.042). In survivors of African ancestry, rs6689879*C showed a 5.43-fold risk of cardiomyopathy and 1.31-fold risk in those of European ancestry. Among survivors of African ancestry with rs6689879*C and CTCAE grade 2-4 cardiomyopathy, the promoter region was hypomethylated. Similar results were observed in survivors of European ancestry, albeit with reduced magnitudes of hypomethylation among those with rs6689879*C and CTCAE grade 2-4 cardiomyopathy. was upregulated in human-induced pluripotent stem cell-derived cardiomyocytes from patients with doxorubicin-induced cardiomyopathy. These findings have potential implications for long-term cardiac surveillance and up-front cancer care for patients of African ancestry. SIGNIFICANCE: Childhood cancer survivors of African ancestry are at higher risk of cardiomyopathy than those of European ancestry, and a novel locus at 1p13.2 is associated with therapy-related cardiomyopathy specifically in African-American survivors.. - Source: PubMed
Publication date: 2020/12/07
Sapkota YadavQin NaEhrhardt Matthew JWang ZhaomingChen YanWilson Carmen LEstepp JeremieRai ParulHankins Jane SBurridge Paul WJefferies John LZhang JinghuiHudson Melissa MRobison Leslie LArmstrong Gregory TMulrooney Daniel AYasui Yutaka - Pemphigus foliaceus (PF) is an autoimmune skin disease characterized by autoantibodies directed mainly against desmoglein-1. The purpose of this study was to determine whether differential susceptibility to endemic PF in Brazil (fogo selvagem) is associated with polymorphisms at the cytogenetic location 1p13.2. Four single nucleotide polymorphisms that together tag 28 SNPs on a segment of approximately 312,000 bp encompassing the protein-coding genes MAGI3, PHTF1, RSBN1, PTPN22, BCL2L15, AP4B1, DCLRE1B, the pseudogenes MTND5P20, RPS2P14 (AL133517.1) and the long non-coding RNA genes AL137856.1, and AP4B1-AS1 were used as markers for association analysis in a case-control study. Allele, genotype and haplotype frequencies of rs33996649, rs2476601, rs3789604 and rs3195954 were compared between patient and control samples. No significant association was found. Lack of association with rs2476601 of the PTPN22 gene agrees with previous results for pemphigus vulgaris and the Tunisian form of endemic pemphigus foliaceus. The other three SNPs had never been analysed before in any form of pemphigus. We conclude that variants in structural and regulatory sites of region 1p13.2 are not susceptibility factors for fogo selvagem. We suggest careful investigation of this genomic region in diseases that had been previously associated with PTPN22, since there are several other genes relevant for immune-mediated diseases located in 1p13.2. - Source: PubMed
Publication date: 2019/03/18
Lobo-Alves Sara Cristinade Oliveira Liana AlvesPetzl-Erler Maria Luiza