Identification and characterization of human GDF15 knockouts.

Growth differentiation factor 15 (GDF15) is a secreted protein that regulates food intake, body weight and stress responses in pre-clinical models. The physiological function of GDF15 in humans remains unclear. Pharmacologically, GDF15 agonism in humans causes nausea without accompanying weight loss, and GDF15 antagonism is being tested in clinical trials to treat cachexia and anorexia.

Determinants for the development of creative tourism: A stakeholder perspective.

This study aims to investigate the determinants that contribute to the sustainable development of creative tourism, a transformative shift from traditional cultural tourism which possess high economic potential. Grounded in stakeholder theory, a qualitative approach was employed to explore the perspectives of 23 existing suppliers of creative tourism in the Greater Bay Area, China, through semi-structured, in-depth interviews with key management in exiting business, this study uncovers determinants for the development of creative tourism. The findings shed light on the significance of fostering creative synergies and their implications for sustainable growth in the industry.

Association of the End-Stage Renal Disease Treatment Choices Payment Model With Home Dialysis Use at Kidney Failure Onset From 2016 to 2022.

Importance: The Centers for Medicare & Medicaid Services designed a mandatory payment model to incentivize home dialysis use: the End-Stage Renal Disease Treatment Choices (ETC). Outpatient dialysis facilities and health care professionals providing nephrology services were randomly assigned to ETC participation at the hospital referral region level.

Objective: To assess the association between ETC and home dialysis use in the incident dialysis population in its first 18 months of implementation.

SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile.

Purpose: This study aimed to undertake a multidisciplinary characterization of the phenotype associated with SOX11 variants.

Methods: Individuals with protein altering variants in SOX11 were identified through exome and genome sequencing and international data sharing. Deep clinical phenotyping was undertaken by referring clinicians.

Inducing wellbeing through staycation programs in the midst of the COVID-19 crisis.

The COVID-19 pandemic aftermath has aggravated its traumatic effect to engender a mental health crisis. With increasingly worsened psychological wellbeing, it is the responsibility of tourism scholars and operators alike to explore how contemporary tourism offerings can enable individuals to rebuild hope and optimism through relishing tourism's restorative appeals amid rigid border lockdowns. However, it remains unclear whether tourists are able to restore themselves from staycation programs, since tourists have a tendency to favor a novel space, as opposed to a usual travel environment.

Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use.

Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.

Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.

The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.

Association of Susceptibility Genes for Adolescent Idiopathic Scoliosis and Intervertebral Disc Degeneration With Adult Spinal Deformity.

Study Design: Genetic case-control study of single nucleotide polymorphisms (SNPs).

Objective: To examine the association of previously reported susceptibility genes for adolescent idiopathic scoliosis (AIS) and intervertebral disc (IVD) degeneration with adult spinal deformity (ASD).

Summary Of Background Data: ASD is a spinal deformity that develops and progresses with age.

Bi-allelic loss of function variants of causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis.

Background: Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms in have been reported as a disease-causing model of CS.

A multiethnic meta-analysis defined the association of rs12946942 with severe adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common type of scoliosis. Controlling its curve progression is the most important clinical task. Although recent genome-wide association studies (GWASs) identified several susceptibility loci associated with the development of AIS, the etiology of curve progression has been still unknown.

Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci.

Adolescent idiopathic scoliosis (AIS) is the most common musculoskeletal disorder of childhood development. The genetic architecture of AIS is complex, and the great majority of risk factors are undiscovered. To identify new AIS susceptibility loci, we conducted the first genome-wide meta-analysis of AIS genome-wide association studies, including 7956 cases and 88 459 controls from 3 ancestral groups.

Screening of known disease genes in congenital scoliosis.

Background: Congenital scoliosis (CS) is defined as a lateral curvature of the spine due to the vertebral malformations and has an incidence of 0.5-1/1,000 births. We previously examined TBX6 in Japanese CS patients and revealed that approximately 10% of CS was caused by TBX6 mutations.

A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.

CELSR2 is a candidate susceptibility gene in idiopathic scoliosis.

A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene.

A functional variant in MIR4300HG, the host gene of microRNA MIR4300 is associated with progression of adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity affecting millions of children. Since treatment and prognosis of AIS depend on curve progression, identifying factors related to AIS curve progression is important in its management. Although several genetic loci for AIS occurrence are reported, no locus for curve progression has been identified.

Response to Lefebvre et al.

Congenital scoliosis (CS) is a common vertebral malformation with incidence of up to 1 of 1000 births worldwide. Recently, TBX6 has been reported as the first disease gene for CS: about 10% of CS patients are compound heterozygotes of rare null mutations and a common haplotype composed by 3 SNPs in TBX6. Lefebvre et al in this journal reported that 2 patients with spondylocostal dysostosis (SCD), a rare skeletal dysplasia affecting spine and ribs also have TBX6 mutations: 1 carried the microdeletion and a rare missense variant, and another 2 rare missense variants.

A Replication Study for the Association of rs11190870 With Curve Severity in Adolescent Idiopathic Scoliosis in Japanese.

Study Design: Case-only study.

Objective: The aim of this study was to confirm the association of rs11190870 with adolescent idiopathic scoliosis (AIS) severity in Japanese patients with AIS.

Summary Of Background Data: Although the association of rs11190870 with AIS susceptibility is replicated in multiple ethnics, the association of rs11190870 with curve severity is controversial.

Compound Heterozygosity for Null Mutations and a Common Hypomorphic Risk Haplotype in TBX6 Causes Congenital Scoliosis.

Congenital scoliosis (CS) occurs as a result of vertebral malformations and has an incidence of 0.5-1/1,000 births. Recently, TBX6 on chromosome 16p11.

Identification and Functional Characterization of RSPO2 as a Susceptibility Gene for Ossification of the Posterior Longitudinal Ligament of the Spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common spinal disorder that results from ectopic ossification of the posterior longitudinal ligament and causes intractable myelopathy and radiculopathy. In a previous genome-wide association study (GWAS), we found six loci associated with OPLL; however, susceptibility genes in these loci have not been identified yet. Here, we examined one of the GWAS loci and identified RSPO2 (encoding R-spondin 2) as a susceptibility gene for OPLL.

[Genome-wide association study for adolescent idiopathic scoliosis].

Adolescent idiopathic scoliosis(AIS)is a polygenic disease. Genome-wide association studies(GWASs)have been performed for a lot of polygenic diseases. For AIS, we conducted GWAS and identified the first AIS locus near LBX1.

Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations.

Axial spondylometaphyseal dysplasia (axial SMD) is an autosomal recessive disease characterized by dysplasia of axial skeleton and retinal dystrophy. We conducted whole exome sequencing and identified C21orf2 (chromosome 21 open reading frame 2) as a disease gene for axial SMD. C21orf2 mutations have been recently found to cause isolated retinal degeneration and Jeune syndrome.

Functional Investigation of a Non-coding Variant Associated with Adolescent Idiopathic Scoliosis in Zebrafish: Elevated Expression of the Ladybird Homeobox Gene Causes Body Axis Deformation.

Previously, we identified an adolescent idiopathic scoliosis susceptibility locus near human ladybird homeobox 1 (LBX1) and FLJ41350 by a genome-wide association study. Here, we characterized the associated non-coding variant and investigated the function of these genes. A chromosome conformation capture assay revealed that the genome region with the most significantly associated single nucleotide polymorphism (rs11190870) physically interacted with the promoter region of LBX1-FLJ41350.