phenome-wide association study

BACKGROUND: Thyroid cancer represents the most prevalent malignant endocrine tumour, with rising incidence worldwide and high mortality rates among patients exhibiting dedifferentiation and metastasis. Effective biomarkers and therapeutic interventions are warranted in aggressive thyroid malignancies. The transcription factor 19 (TCF19) gene has been implicated in conferring a malignant phenotype in cancers. However, its contribution to thyroid neoplasms remains unclear. RESULTS: In this study, we performed genome-wide and phenome-wide association studies to identify a potential causal relationship between TCF19 and thyroid cancer...

BACKGROUND: Ankylosing Spondylitis (AS) is a chronic inflammatory disorder which can lead to considerable pain and disability. Mendelian randomization (MR) has been extensively applied for repurposing licensed drugs and uncovering new therapeutic targets. Our objective is to pinpoint innovative therapeutic protein targets for AS and assess the potential adverse effects of druggable proteins. METHODS: We conducted a comprehensive proteome-wide MR study to assess the causal relationships between plasma proteins and the risk of AS...

BACKGROUND: Male-pattern baldness (MPB) is the most common cause of hair loss in men. It can be categorized into three types: type 2 (T2), type 3 (T3), and type 4 (T4), with type 1 (T1) being considered normal. Although various MPB-associated genetic variants have been suggested, a comprehensive study for linking these variants to gene expression regulation has not been performed to the best of our knowledge. RESULTS: In this study, we prioritized MPB-related tissue panels using tissue-specific enrichment analysis and utilized single-tissue panels from genotype-tissue expression version 8, as well as cross-tissue panels from context-specific genetics...

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is often comorbid with other medical conditions in adult patients. However, ADHD is extremely underdiagnosed in adults and little is known about the medical comorbidities in undiagnosed adult individuals with high ADHD liability. In this study we investigated associations between ADHD genetic liability and electronic health record (EHR)-based ICD-10 diagnoses across all diagnostic categories, in individuals without ADHD diagnosis history...

Chenopodium quinoa manifests adaptability to grow under varying agro-climatic scenarios. Assessing quinoa germplasm's phenotypic and genetic variability is a prerequisite for introducing it as a potential candidate in cropping systems. Adaptability is the basic outcome of ecological genomics of crop plants. Adaptive variation predicted with a genome-wide association study provides a valuable basis for marker-assisted breeding. Hence, a panel of 72 quinoa plants was phenotyped for agro morphological attributes and association-mapping for distinct imperative agronomic traits...

The dermis and epidermis, crucial structural layers of the skin, encompass appendages, hair follicles (HFs), and intricate cellular heterogeneity. However, an integrated spatiotemporal transcriptomic atlas of embryonic skin has not yet been described and would be invaluable for studying skin-related diseases in humans. Here, single-cell and spatial transcriptomic analyses are performed on skin samples of normal and hairless fetal pigs across four developmental periods. The cross-species comparison of skin cells illustrated that the pig epidermis is more representative of the human epidermis than mice epidermis...

Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues; both addiction and the attribution of incentive salience are influenced by environmental and genetic factors. To characterize the genetic contributions to incentive salience attribution, we performed a genome-wide association study (GWAS) in a cohort of 1,645 genetically diverse heterogeneous stock (HS) rats. We tested HS rats in a Pavlovian conditioned approach task, in which we characterized the individual responses to food-associated stimuli ("cues")...

Bipolar disorder is a chronic and complex polygenic disease with high rates of comorbidity. However, the independent contribution of either diagnosis or genetic risk of bipolar disorder to the medical comorbidity profile of individuals with the disease remains unresolved. Here, we conducted a multi-step phenome-wide association study (PheWAS) of bipolar disorder using phenomes derived from the electronic health records of participants enrolled in the Mayo Clinic Biobank and the Mayo Clinic Bipolar Disorder Biobank...

Osteoarthritis (OA) is a common degenerative disease. Although some biomarkers and drug targets of OA have been discovered and employed, limitations and challenges still exist in the targeted therapy of OA. Mendelian randomization (MR) analysis has been regarded as a reliable analytic method to identify effective therapeutic targets. Thus, we aimed to identify novel therapeutic targets for OA and investigate their potential side effects based on MR analysis. In this study, two-sample MR, colocalization analysis, summary-data-based Mendelian randomization (SMR) and Mendelian randomization phenome-wide association study (MR-PheWAS) were conducted...

BACKGROUND: Individuals with osteoarthritis present with comorbidities, and the potential causal associations remain incompletely elucidated. The present study undertook a large-scale investigation about the causality between osteoarthritis and variable traits, using the summary-level data of genome-wide association studies (GWAS). METHODS: The present study included the summary-level GWS data of knee osteoarthritis, hip osteoarthritis, hip or knee osteoarthritis, hand osteoarthritis, and other 1355 traits...

For many cancers there are only a few well-established risk factors. Here, we use summary data from genome-wide association studies (GWAS) in a Mendelian randomisation (MR) phenome-wide association study (PheWAS) to identify potentially causal relationships for over 3,000 traits. Our outcome datasets comprise 378,142 cases across breast, prostate, colorectal, lung, endometrial, oesophageal, renal, and ovarian cancers, as well as 485,715 controls. We complement this analysis by systematically mining the literature space for supporting evidence...

The study aimed to investigate the clinical significance of the interaction between hypoxia and the immune system in esophageal squamous cell carcinoma (ESCC) microenvironment. A comprehensive evaluation of 13 hypoxia phenotype-related genes (HPRs) was conducted using data from TCGA-ESCC and two GEO cohorts. Three distinct HPRclusters were identified, and the HPRscore was established as an independent prognostic factor ( p = 0.001), with higher scores indicating poorer prognosis. The HPRscore was validated in various immunotherapy cohorts, demonstrating its efficacy in evaluating immunotherapy and chemotherapy outcomes...

Hyperparathyroidism (HPT) manifests as a complex condition with a substantial disease burden. While advances have been made in surgical interventions and non-surgical pharmacotherapy for the management of hyperparathyroidism, radical options to halt underlying disease progression remain lacking. Identifying putative genetic drivers and exploring novel drug targets that can impede HPT progression remain critical unmet needs. A Mendelian randomization (MR) analysis was performed to uncover putative therapeutic targets implicated in hyperparathyroidism pathology...

There is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14,819 cases among 941,863 participants of European ancestry. We report 32 genomic loci, among which 20 are novel. RNA sequencing of 500 human aortic valves highlights an enrichment in expression regulation at these loci and prioritizes candidate causal genes...

BACKGROUND: Numerous observational studies have highlighted associations of genetic predisposition of head and neck squamous cell carcinoma (HNSCC) with diverse risk factors, but these findings are constrained by design limitations of observational studies. In this study, we utilized a phenome-wide association study (PheWAS) approach, incorporating a polygenic risk score (PRS) derived from a wide array of genomic variants, to systematically investigate phenotypes associated with genetic predisposition to HNSCC...

BACKGROUND: The gene variants ADH1B*2 (Arg48His, rs1229984) and ALDH2*2 (Glu504Lys, rs671) are common in East Asian populations but rare in other populations. We propose that selective pressures from pathogen exposure and dietary changes during the neolithic transition favored these variants. Thus, their current association with differences in alcohol sensitivity likely results from phenotypic plasticity rather than direct natural selection. METHODS: Samples sourced from the Allele Frequency Database (ALFRED) were utilized to compute the average frequency of ADH1B*2 and ALDH2*2 across 88 and 61 countries, respectively...

BACKGROUND: Ovarian cancer (OC) is commonly diagnosed among older women who have comorbidities. This hypothesis-free phenome-wide association study (PheWAS) aimed to identify comorbidities associated with OC, as well as traits that share a genetic architecture with OC. METHODS: We used data from 181,203 white British female UK Biobank participants and analysed OC and OC subtype-specific genetic risk scores (OC-GRS) for an association with 889 diseases and 43 other traits...

Gastroesophageal reflux disease (GERD) is a prevalent chronic ailment, and present therapeutic approaches are not always effective. This study aimed to find new drug targets for GERD and Barrett's esophagus (BE). We obtained genetic instruments for GERD, BE, and 2004 plasma proteins from recently published genome-wide association studies (GWAS), and Mendelian randomization (MR) was employed to explore potential drug targets. We further winnowed down MR-prioritized proteins through replication, reverse causality testing, colocalization analysis, phenotype scanning, and Phenome-wide MR...

OBJECTIVES: To explore the associations of long-term exposure to air pollution with onset of all human health conditions. DESIGN: Prospective phenome-wide association study. SETTING: Denmark. PARTICIPANTS: All Danish residents aged ≥30 years on 1 January 2000 were included (N=3 323 612). After exclusion of individuals with missing geocoded residential addresses, 3 111 988 participants were available for the statistical analyses...

SUMMARY: With the rapid growth of genetic data linked to electronic health record data in huge cohorts, large-scale phenome-wide association study (PheWAS), have become powerful discovery tools in biomedical research. PheWAS is an analysis method to study phenotype associations utilizing longitudinal electronic health record (EHR) data. Previous PheWAS packages were developed mostly in the days of smaller biobanks and with earlier PheWAS approaches. PheTK was designed to simplify analysis and efficiently handle biobank-scale data...