Integrative analysis of transcriptome and proteome wide association studies prioritized functional genes for obesity.

Background: Genome-wide association studies have identified dozens of genomic loci for obesity. However, functional genes and their detailed genetic mechanisms underlying these loci are mainly unknown. In this study, we conducted an integrative study to prioritize plausibly functional genes by combining information from genome-, transcriptome- and proteome-wide association analyses.

The genetic architecture of age at menarche and its causal effects on other traits.

Age at menarche (AAM) is a sign of puberty of females. It is a heritable trait associated with various adult diseases. However, the genetic mechanism that determines AAM and links it to disease risk is poorly understood.

Exome-Wide Sequencing Study Identified Genetic Variants Associated With Sarcopenic Obesity.

Sarcopenic obesity (SO) is an age-related disease characterized by the coexistence of excessive adiposity and low muscle mass or function. Although obesity and sarcopenia are heritable conditions, the genetic determinants of SO have not been fully understood. We conducted a large-scale exome-wide association analysis of SO in a sequenced sample of 2 887 cases and 113 284 controls and an imputed sample of 4 003 cases and 161 990 controls in the UK Biobank cohort.

Screening Plasma Proteins for the Putative Drug Targets for Carpal Tunnel Syndrome.

Carpal tunnel syndrome (CTS) is one of the most common work-related musculoskeletal disorders. The present study sought to identify putative causal proteins for CTS. We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal association between 2859 plasma proteins (N = 35,559) and CTS (N = 1,239,680) based on the published GWAS summary statistics.

Effect of vitamin D supplementation in winter on physical performance of university students: a one-month randomized controlled trial.

Background: There is epidemiological evidence which suggests an association between 25-hydroxyvitamin D [25(OH)D] levels and bone and muscle function; however, it is unclear whether vitamin D supplementation has an added benefit beyond bone health. Here, we investigated the effects of vitamin D supplementation (1 month) on physical performance in Chinese university students in winter.

Methods: One hundred and seventeen eligible subjects with 25(OH)D (19.

Causal associations between type 1 diabetes and COVID-19 infection and prognosis: a two-sample Mendelian randomization study.

Introduction: It has been suggested that type 1 diabetes was associated with increased COVID-19 morbidity and mortality. However, their causal relationship is still unclear. Herein, we performed a two-sample Mendelian randomization (MR) to investigate the causal effect of type 1 diabetes on COVID-19 infection and prognosis.

Proteome and genome integration analysis of obesity.

The prevalence of obesity has increased worldwide in recent decades. Genetic factors are now known to play a substantial role in the predisposition to obesity and may contribute up to 70% of the risk for obesity. Technological advancements during the last decades have allowed the identification of many hundreds of genetic markers associated with obesity.

Causal Effects of Plasma Proteome on Osteoporosis and Osteoarthritis.

The two-sample Mendelian randomization (MR) study revealed a causal association of plasma proteins with osteoporosis (OP) and osteoarthritis (OA). Bone mineral density (BMD) is the gold standard for the clinical assessment of OP. Recent studies have shown that plasma proteins play an essential role in the regulation of bone development.

Efficient identification of trait-associated loss-of-function variants in the UK Biobank cohort by exome-sequencing based genotype imputation.

The large-scale open access whole-exome sequencing (WES) data of the UK Biobank ~200,000 participants is accelerating a new wave of genetic association studies aiming to identify rare and functional loss-of-function (LoF) variants associated with complex traits and diseases. We proposed to merge the WES genotypes and the genome-wide genotyping (GWAS) genotypes of 167,000 UKB homogeneous European participants into a combined reference panel, and then to impute 241,911 UKB homogeneous European participants who had the GWAS genotypes only. We then used the imputed data to replicate association identified in the discovery WES sample.

Gut Microbiota and Psychiatric Disorders: A Two-Sample Mendelian Randomization Study.

Evidence supports the observational associations of gut microbiota with a variety of psychiatric disorders, but the causal nature of such associations remains obscure. Aiming to comprehensively investigate their causal relationship and to identify specific causal microbe taxa for psychiatric diseases, we conducted a two-sample Mendelian randomization (MR) analysis of gut microbiome with 15 psychiatric diseases. Specifically, the microbiome genome-wide association study (GWAS) in 18,473 individuals from the MiBioGen study was used as exposure sample, and the GWAS for 15 psychiatric diseases was used as outcome samples.

Prediction of Clinical Outcome in Endometrial Carcinoma Based on a 3-lncRNA Signature.

Endometrial carcinoma (EC) is one of the common gynecological cancers with increasing incidence and revived mortality recently. Given the heterogeneity of tumors and the complexity of lncRNAs, a panel of lncRNA biomarkers might be more precise and stable for prognosis. In the present study, we developed a new lncRNA model to predict the prognosis of patients with EC.

Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization Study.

Background: Growing evidence has shown that alterations in gut microbiota composition are associated with multiple autoimmune diseases (ADs). However, it is unclear whether these associations reflect a causal relationship.

Objective: To reveal the causal association between gut microbiota and AD, we conducted a two-sample Mendelian randomization (MR) analysis.

Causal relationship between gut microbiota and serum vitamin D: evidence from genetic correlation and Mendelian randomization study.

Background: The gastrointestinal microbiota is emerging as an important mediator in intestinal metabolism, such as vitamin D absorption.

Methods: To elucidate the causality of microbiota and vitamin D, we used linkage disequilibrium score (LDSC) regression and two-sample Mendelian randomization (MR) methods with largest genome-wide association study (GWAS) summary statistics to identify specific taxa that are linked to serum 25-hydroxyvitamin D (25(OH)D).

Results: We found that Ruminiclostridium9 was significantly genetically correlated with 25(OH)D at nominal significance (r = 0.

Mendelian Randomization Analysis Reveals Causal Effects of Plasma Proteome on Body Composition Traits.

Context: Observational studies have demonstrated associations between plasma proteins and obesity, but evidence of causal relationship remains to be studied.

Objective: We aimed to evaluate the causal relationship between plasma proteins and body composition.

Methods: We conducted a 2-sample Mendelian randomization (MR) analysis based on the genome-wide association study (GWAS) summary statistics of 23 body composition traits and 2656 plasma proteins.

Joint Genome-Wide Association Analyses Identified 49 Novel Loci For Age at Natural Menopause.

Background: Age at natural menopause (ANM) is an important index for women's health. Either early or late ANM is associated with a series of adverse outcomes later in life. Despite being an inheritable trait, its genetic determinant has not yet been fully understood.

Mendelian Randomization Analysis Reveals Causal Effects of the Human Gut Microbiota on Abdominal Obesity.

Background: Although recent studies have revealed an association between the composition of the gut microbiota and obesity, whether specific gut microbiota cause obesity has not been determined.

Objectives: The aim of this study is to determine the causal relationship between specific gut microbiota and abdominal obesity. Based on genome-wide association study (GWAS) summary statistics, we performed a 2-sample Mendelian randomization (MR) analysis to evaluate whether the gut microbiota affects abdominal obesity.

The genetic architecture of appendicular lean mass characterized by association analysis in the UK Biobank study.

Appendicular lean mass (ALM) is a heritable trait associated with loss of lean muscle mass and strength, or sarcopenia, but its genetic determinants are largely unknown. Here we conducted a genome-wide association study (GWAS) with 450,243 UK Biobank participants to uncover its genetic architecture. A total of 1059 conditionally independent variants from 799 loci were identified at the genome-wide significance level (p < 5 × 10), all of which were also significant at p < 5 × 10 in both sexes.

Assessing causal relationship from gut microbiota to heel bone mineral density.

Recent studies have demonstrated the important role played by gut microbiota in regulating bone development, but the evidence of such causal relationship is still sparse in human population. The aim of this study is to assess the causal relationship from gut microbiota to bone development and to identify specific causal bacteria taxa via a Mendelian randomization (MR) approach. A genome-wide association study (GWAS) summary statistic based two-sample MR analysis was performed.

Three pleiotropic loci associated with bone mineral density and lean body mass.

Both bone mineral density (BMD) and lean body mass (LBM) are important physiological measures with strong genetic determination. Besides, BMD and LBM might have common genetic factors. Aiming to identify pleiotropic genomic loci underlying BMD and LBM, we performed bivariate genome-wide association study meta-analyses of femoral neck bone mineral density and LBM at arms and legs, and replicated in the large-scale UK Biobank cohort sample.

Identification of pleiotropic loci underlying hip bone mineral density and trunk lean mass.

Bone mineral density (BMD) and lean body mass (LBM) not only have a considerable heritability each, but also are genetically correlated. However, common genetic determinants shared by both traits are largely unknown. In the present study, we performed a bivariate genome-wide association study (GWAS) meta-analysis of hip BMD and trunk lean mass (TLM) in 11,335 subjects from 6 samples, and performed replication in estimated heel BMD and TLM in 215,234 UK Biobank (UKB) participants.