Mendelian randomization (MR) uses genetic variation as a natural experiment to investigate the causal effects of modifiable risk factors (exposures) on outcomes. Two-sample Mendelian randomization (2SMR) is widely used to measure causal effects between exposures and outcomes via genome-wide association studies. 2SMR can increase statistical power by utilizing summary statistics from large consortia such as the UK Biobank. However, the first-order term approximation of standard error is commonly used when applying 2SMR. This approximation can underestimate the variance of causal effects in MR, which can lead to an increased false-positive rate. An alternative is to use the second-order approximation of the standard error, which can considerably correct for the deviation of the first-order approximation. In this study, we simulated MR to show the degree to which the first-order approximation underestimates the variance. We show that depending on the specific situation, the first-order approximation can underestimate the variance almost by half when compared to the true variance, whereas the second-order approximation is robust and accurate.

Current anatomy education in Korea has been dependent upon foreign textbooks and atlas. Various models and medical devices commonly used in Korea were imported from overseas. Now, it is necessary to design, produce and supply medical education, operative tools and treatment supportive devices customized to Korean human body and constitution. Accordingly, this is the time to assemble and deliver medical data to Korean population. Indivicess from the measurement for various types of bones were calculated, and the results were compared with data from foreign atlas and pictures. Individual drawings of bones from sacrum, hip bone and lower limb were made by using parameters we calculated, thus the atlas of Korean skeleton was constructed from artistic anatomical point of view. As a result, there were significant differences between Korean skeletons and the medical drawings from the oversea edition, and also we found numerous exaggerated and false dimensions without actual measurement. In the present study, we primarily focused on building musculoskeletal system of Korea population and set our goal as utilizing its graphic data for medical education in Korea. The present study would be the first study preparing theoretical foundations of Korean skeletal graphic system based on Korean body shape by comparison with other ethnic groups and foreign graphical models. Simultaneously, we conducted practical construction of the skeletal atlas by employing Korean standard measure data.
Constitution and Bylaws ; Education ; Education, Medical ; Ethnic Groups ; Foundations ; Hip* ; Human Body ; Humans ; Korea ; Lower Extremity* ; Musculoskeletal System ; Sacrum ; Skeleton*

Saponin has been known to be a major antioxidant component in panax ginseng. Recent experimental study suggests that some antioxidant materials prevent Parkinson's disease caused by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in an animal model. The present study was performed to demonstrate the effect of ginseng saponins in the Parkinson's disease model induced by MPTP. To verify the effect of ginseng saponin on dopaminergic neurons in the mice brain, the tyrosine hydroxylase-immunoreactive (TH-ir) neurons were observed by immunohistochemical stain and immunoelectron microscopy (preembedding method). Also, in order to estimate the immunoreactivity of dopaminergic neuropils, they were quantified by image analysis. The number of TH-ir neurons of substantia nigra was significantly increased in the high-dose (0.46 mg/kg) ginseng saponin group compared with the MPTP injected group. The immunoreactivity of TH-ir neuropils in striatum was significantly increased in both high and low-dose (0.1 mg/kg) ginseng saponin groups compared with the MPTP injected group. In immunoelectron microscopic observation, TH-ir neurons of the control and both ginseng saponin injected group showed normal nuclei and well preserved cytoplasmic organelles. In the MPTP injected group, dying dopaminergic neurons showed destroyed nuclei and cytoplasmic organelles. These results suggest that ginseng saponin has a protective effect on the Parkinson's disease model induced by MPTP.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Brain ; Cytoplasm ; Dopaminergic Neurons* ; Mice* ; Microscopy, Immunoelectron ; Models, Animal ; Neurons ; Neuropil ; Organelles ; Panax* ; Parkinson Disease* ; Saponins* ; Substantia Nigra ; Tyrosine ; Tyrosine 3-Monooxygenase

Recently developed computational methods allow the imputation of human leukocyte antigen (HLA) genes using intergenic single nucleotide polymorphism markers. To improve the imputation accuracy in HLA imputation, it is essential to increase the sample size and the diversity of alleles in the reference panel. Our software, MergeReference, helps achieve this goal by providing a streamlined pipeline for combining multiple reference panels into one.
Alleles ; HLA Antigens ; Humans ; Leukocytes ; Major Histocompatibility Complex ; Polymorphism, Single Nucleotide ; Sample Size

The meta-analysis has become a widely used tool for many applications in bioinformatics, including genome-wide association studies. A commonly used approach for meta-analysis is the fixed effects model approach, for which there are two popular methods: the inverse variance-weighted average method and weighted sum of z-scores method. Although previous studies have shown that the two methods perform similarly, their characteristics and their relationship have not been thoroughly investigated. In this paper, we investigate the optimal characteristics of the two methods and show the connection between the two methods. We demonstrate that the each method is optimized for a unique goal, which gives us insight into the optimal weights for the weighted sum of z-scores method. We examine the connection between the two methods both analytically and empirically and show that their resulting statistics become equivalent under certain assumptions. Finally, we apply both methods to the Wellcome Trust Case Control Consortium data and demonstrate that the two methods can give distinct results in certain study designs.
Case-Control Studies ; Computational Biology ; Genome-Wide Association Study ; Methods* ; Weights and Measures

Current anatomy education in Korea has been dependent upon foreign textbooks and atlas. Various models and medical devices from overseas were imported and commonly used in Korea, Now, we need to provide our own literatures and graphic data based on Korean population for student education. It is necessary to design, produce and supply medical education, operative tools and treatment supportive devices customized to Korean human body and constitution. Accordingly, this is the time to assemble and deliver medical data to Korean population. In this study, we primarily focused on building musculoskeletal system of Korea population and set our goal as utilizing its graphic data for medical education in Korea. It is first study preparing theoretical foundations of Korean skeletal graphic system based on Korean body shape by comparison with other ethnic groups and foreign graphical models. Simultaneously, we conducted practical construction of the skeletal atlas by employing Korean standard measures. Parameters from the measurement for various types of bones were calculated, and the results were compared with data from foreign atlas and pictures. Individual drawings of bones from skull, upper extremity was made by using parameters we calculated, thus the atlas of Korean skeleton was constructed from artistic anatomical point of view. As a result, there were significant differences between Korean skeletons and the medical drawings from the oversea edition. Because many foreign drawings used data from Caucasians only and there were numerous exaggerated and false dimensions without actual measurement. In conclusion, the result of the study is expected to provide fundamental data for building anatomical atlas about Korean human body structure.
Constitution and Bylaws ; Education ; Education, Medical ; Ethnic Groups ; Foundations ; Human Body ; Humans ; Korea ; Musculoskeletal System ; Skeleton* ; Skull ; Upper Extremity*

BACKGROUND AND OBJECTIVES: Food restriction increases life span, reduces aging rate and affects a wide variety of biological functions. Neurotransmitter is a substance released from the axon terminal of a presynaptic neuron on excitation, which diffuses across the synaptic cleft to either excite or inhibit the target cell. The nervous system makes use of neurotransmitters for signaling. We investigated the change of immunoreactivity of neuropeptides in olfactory bulb of rat after food restriction. MATERIALS AND METHOD: Of 10-week old Sprague-Dawley rats used in this study. six rats were killed at the beginning of the experiment. Thirty rats which had been restricted to only half of their normal voluntary mean food intake (12 g instead of 24 g per day) were killed at 3 days, 1, 2, 4 and 9 weeks after food restriction (n=6 per time point). Olfactory bulbs of the rats were cut into 40 micrometer-thick coronal sections and immunostained. RESULTS: On the layers of glomerular, outer plexiform, granular cell and subependymal zone of olfactory bulb, immunoreactivities of cholecystokinin (CCK), tyrosine hydrolase (TH), and neuropeptide-Y (NPY) were increased at one week of food restriction. On all layers, immunoreactivities of CCK and TH were increased at 2 weeks of food restriction. However, immunoreactivity of NPY was increased on the only layers of glomerular, and granular cell of olfactory bulb at week 2. After 4th week, the immunoreactivity of NPY was the same as the control group; after 9th week, the mmunoreactivity of CCK and TH were the same as the control group. CONCLUSION: Our results demonstrated that CCK, TH, and NPY could be expressed in different manners on the layers of olfactory bulb of rat after food restriction, and that food restriction may improve olfactory sensitivity owing to the change of neuropeptides.
Aging ; Animals ; Cholecystokinin ; Eating ; Nervous System ; Neurons ; Neuropeptides* ; Neurotransmitter Agents ; Olfactory Bulb* ; Presynaptic Terminals ; Rats* ; Rats, Sprague-Dawley ; Tyrosine

The Wellcome Trust Case Control Consortium (WTCCC) study was a large genome-wide association study that aimed to identify common variants associated with seven diseases. That study combined two control datasets (58C and UK Blood Services) as shared controls. Prior to using the combined controls, the WTCCC performed analyses to show that the genomic content of the control datasets was not significantly different. Recently, the analysis of human leukocyte antigen (HLA) genes has become prevalent due to the development of HLA imputation technology. In this project, we extended the between-control homogeneity analysis of the WTCCC to HLA. We imputed HLA information in the WTCCC control dataset and showed that the HLA content was not significantly different between the two control datasets, suggesting that the combined controls can be used as controls for HLA fine-mapping analysis based on HLA imputation.
Case-Control Studies ; Dataset ; Genome-Wide Association Study ; Humans ; Leukocytes

Background/Aims: Lung function is an objective indicator of diagnosis and prognosis of respiratory diseases. Many common genetic variants have been associated with lung function in multiple ethnic populations. We looked for coding variants associated with forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) in the Korean general population. Methods: We carried out exome array analysis and lung function measurements of the FEV1 and FEV1/FVC in 7,524 individuals of the Korean population. We evaluated single variants with minor allele frequency greater than 0.5%. We performed look-ups for candidate coding variants associations in the UK Biobank, SpiroMeta, and CHARGE consortia. Results: We identified coding variants in the SMIM29 (C6orf1) (p = 1.2 × 10–5) and HMGA1 locus on chromosome 6p21, the GIT2 (p = 6.5 × 10–5) locus on chromosome 12q24, and the ARHGEF40 (p = 9.9 × 10–5) locus on chromosome 14q11 as having a significant association with lung function (FEV1). We also confirmed a previously reported association with lung function and chronic obstructive pulmonary disease in the FAM13A (p = 4.54 × 10–6) locus on chromosome 4q22, in TNXB (p = 1.30 × 10–6) and in AGER (p = 1.09 × 10–8) locus on chromosome 6p21. Conclusions Our exome array analysis identified that several protein coding variants were associated with lung function in the Korean population. Common coding variants in SMIM29 (C6orf1), HMGA1, GIT2, FAM13A, TNXB, AGER and low-frequency variant in ARHGEF40 potentially affect lung function, which warrant further study.

Fulminant type 1 diabetes (T1DM) is a distinct subtype of T1DM that is characterized by rapid onset hyperglycemia, ketoacidosis, absolute insulin deficiency, and near normal levels of glycated hemoglobin at initial presentation. Although it has been reported that class II human leukocyte antigen (HLA) genotype is associated with fulminant T1DM, the genetic predisposition is not fully understood. In this study we investigated the HLA genotype and haplotype in 11 Korean cases of fulminant T1DM using imputation of whole exome sequencing data and compared its frequencies with 413 participants of the Korean Reference Panel. The HLA-DRB1*04:05-HLA-DQB1*04:01 haplotype was significantly associated with increased risk of fulminant T1DM in Fisher's exact test (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.56 to 10.86; p = 0.009). A histidine residue at HLA-DRbeta1 position 13 was marginally associated with increased risk of fulminant T1DM (OR, 2.45; 95% CI ,1.01 to 5.94; p = 0.054). Although we had limited statistical power, we provide evidence that HLA haplotype and amino acid change can be a genetic risk factor of fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.
Autoimmunity ; Exome ; Genetic Predisposition to Disease ; Genotype* ; Haplotypes ; Hemoglobin A, Glycosylated ; Histidine ; HLA Antigens ; Humans ; Hyperglycemia ; Insulin ; Ketosis ; Leukocytes ; Risk Factors