Genome-wide association and replication studies for handedness in a Korean community-based cohort

Introduction: Handedness is a conspicuous characteristic in human behavior, with a worldwide proportion of approximately 90% of people preferring to use the right hand for many tasks. In the Korean population, the proportion of left-handedness is relatively low at approximately 7%-10%, similar to that in other East-Asian cultures in which the use of the left hand for writing and other public activities has historically been oppressed. Methods: In this study, we conducted two genome-wide association studies (GWASs) between right-handedness and left-handedness, and between right-handedness and ambidexterity using logistic regression analyses using a Korean community-based cohort. We also performed association analyses with previously reported variants and our findings. Results: A total of 8806 participants were included for analysis, and the results identified 28 left-handedness-associated and 15 ambidexterity-associated loci; of these, two left-handedness loci (NEIL3 [rs11726465] and SVOPL [rs117495448]) and one ambidexterity locus (PDE8B/WDR41 [rs118077080]) showed near genome-wide significance. Association analyses with previously reported variants replicated ANKS1B (rs7132513) in left-handedness and ANKIB1 (rs2040498) in ambidexterity. Conclusion: The variants and positional candidate genes identified and replicated in this study were largely associated with brain development, cerebral asymmetry, neurological processes, and neuropsychiatric diseases in line with previous findings. As the first East-Asian GWAS related to handedness, these results may provide an intriguing reference for further human neurologic research in the future.ope

Association Between C-Reactive Protein and Metabolic Syndrome in Korean Adults

Background: The prevalence of metabolic syndrome (MetS) is increasing, and obesity, insulin resistance, and inflammation are the known risk factors. However, results of previous studies regarding the relationship between MetS and inflammation have not been consistent. This study aimed to identify the associations between C-reactive protein (CRP) and MetS and its components in obese and non-obese men and women. Methods: This was a cross-sectional study based on the 6th Korea National Health and Nutrition Examination Survey (2015), and a nationally representative sample of 3,013 Korean adults aged 40-78 years were included. Those with cardiovascular disease, cancer, CRP level >10 mg/L, white blood cell count >10,000/mm3 , chronic kidney disease, and lung/liver disease were excluded. Results: Approximately 11.0%, 50.0%, 8.4%, and 48.8% of non-obese men, obese men, non-obese women, and obese women presented with MetS (P<0.001), respectively. In all four groups, those who presented with MetS or its components showed a higher high-sensitivity (hs-CRP) average than those without. Multivariate regression analysis showed the increased risk of developing MetS with higher quartiles of hs-CRP level in obese (3rd and 4th quartiles: odds ratios [ORs], 3.87 and 2.57, respectively) and non-obese women (4th quartile: OR, 2.63). The different components also showed increased ORs in the four groups. However, no statistically significant trend in the relationship was found in men. Conclusion: Low-grade inflammation may increase the risk of MetS in Korean women independent of adiposity. However, due to the cross-sectional design of the present study, further studies must be conducted to identify the causal relationship between inflammation and metabolic disorders.ope

Association between Breakfast Skipping and Homeostasis Model Assessment of Insulin Resistance and the Atherosclerotic Cardiovascular Disease Risk in Non-Diabetic Korean Adults Aged 40–79 Years

Background: It is reported that the decline in breakfast consumption is associated with diabetes, metabolic disease, and cardiovascular disease. This study analyzed the association between skipping breakfast and the homeostasis model assessment of insulin resistance (HOMA-IR) and atherosclerotic cardiovascular disease (ASCVD) risk among non-diabetic Korean adults aged 40–79 years who did not take medication for hypertension or dyslipidemia. Methods: This study included 1,001 adults from the Sixth Korea National Health and Nutrition Examination Survey in 2015. Participants were classified into two groups based on those who skipped breakfast and those who ate breakfast. Analysis of covariance was performed to compare the average value of HOMA-IR between the two groups. Logistic regression analysis was used to evaluate the relationship between skipping breakfast and HOMA-IR and ASCVD risk. All analyses were performed after adjusting for covariates. Results: There was no significant association between the group that skipped breakfast and HOMA-IR or ASCVD risk. However, the odds ratio of ASCVD risk was 3-fold higher in male in the skipping breakfast group that skipped breakfast than in those that ate breakfast. Conclusion: Previous studies that suggested there was an association between skipping breakfast and ASCVD risk may have been biased as they included individuals taking medication, and thus, this could have led to incorrect results. Therefore, further studies on the association between breakfast consumption and ASCVD risk should consider practical factors that can affect eating habits, such as regular medication use in their analysis.ope

Defining Essential Topics and Procedures for Korean Family Medicine Residency Training

Background: This study aims to create a comprehensive list of essential topics and procedural skills for family medicine residency training in Korea. Methods: Three e-mailed surveys were conducted. The first and second surveys were sent to all board-certified family physicians in the Korean Academy of Family Medicine (KAFM) database via e-mail. Participants were asked to rate each of the topics (117 in survey 1, 36 in survey 2) and procedures (65 in survey 1, 19 in survey 2) based on how necessary it was to teach it and personal experience of utilizing it in clinical practice. Agreement rates of the responses were calculated and then sent to the 32 KAFM board members in survey 3. Opinions on potential cut-off points to divide the items into three categories and the minimum achievement requirements needed to graduate for each category were solicited. Results: Of 6,588 physicians, 256 responded to the first survey (3.89% response rate), 209 out of 6,669 to the second survey (3.13%), and 100% responded to the third survey. The final list included 153 topics and 81 procedures, which were organized into three categories: mandatory, recommended, and optional (112/38/3, 27/33/21). For each category of topics and procedures, the minimum requirement for 3-year residency training was set at 90%/60%/30% and 80%/60%/30%, respectively. Conclusion: This national survey was the first investigation to define essential topics and procedures for residency training in Korean family medicine. The lists obtained represent the opinions of Korean family physicians and are expected to aid in the improvement of family medicine training programs in the new competency-based curriculum.ope

A Patient with Neutropenia and Splenomegaly: A Case Report from Department of Family Medicine in Tertiary Hospital Center

Pancytopenia represents a unique challenge for primary care doctors and its etiological causes encompass various specialties, including hematology and rheumatology. Despite the existence of effective tests such as bone marrow biopsy and immunoassays to rule out the potential causes of pancytopenia, it is often difficult to pinpoint the exact diagnosis. In this case report, we have described such a 'gray zone' patient, who presented with pancytopenia, neutropenia, and splenomegaly, and was being treated for fungal pneumonia before being transferred to Severance Hospital (department of family medicine). As the patient had a 10-year history of multiple, long-term hospital admissions that were having a severely debilitating impact on the quality of life, we performed a partial splenic embolization as a potential cure for the symptoms. Although this induced acute blood count recovery, it failed to prevent eventual mortality from septic shock.ope

Association between triglyceride-glucose index and low-density lipoprotein particle size in korean obese adults

Background: Small dense low-density lipoprotein cholesterol (sdLDL-C) is the lipoprotein marker among the various lipoproteins that is most strongly related to atherosclerosis. Insulin resistance (IR) can alter lipid metabolism, and sdLDL-C is characteristic of diabetic dyslipidemia. Therefore, this study sought to inspect the relationship between the triglyceride-glucose (TyG) index and mean low-density lipoprotein (LDL) particle size. Methods: In this study, a total of 128 adults participated. The correlation coefficients between various lipoproteins and the TyG index were compared using Steiger's Z test and the Spearman correlation. The independent link between the TyG index and mean LDL particle size was demonstrated by multiple linear regression analysis. To identify the TyG index cutoff value for the predominance of sdLDL particles, receiver operating characteristic curves were plotted. Results: Mean LDL particle size correlated more strongly with the TyG index than did very low-density lipoprotein, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Regression analysis demonstrated that mean LDL particle size had a strong association with the TyG index (β coefficient = -0.038, P-value < 0.001). The TyG index optimal cutoff value for sdLDL particle predominance and the corresponding area under the curve (standard error: 0.028, 95% confidence interval: 0.842-0.952) were 8.72 and 0.897, respectively, which were close to the cutoff value of diabetes risk in Koreans. Conclusions: Mean LDL particle size is more strongly correlated with the TyG index than do other lipid parameters. After correcting for confounding variables, mean LDL particle size is independently linked with the TyG index. The study indicates that the TyG index is strongly related to atherogenic sdLDL particles predominance.ope

Understanding the genetic architecture of the metabolically unhealthy normal weight and metabolically healthy obese phenotypes in a Korean population

Understanding the mechanisms underlying the metabolically unhealthy normal weight (MUHNW) and metabolically healthy obese (MHO) phenotypes is important for developing strategies to prevent cardiometabolic diseases. Here, we conducted genome-wide association studies (GWASs) to identify the MUHNW and MHO genetic indices. The study dataset comprised genome-wide single-nucleotide polymorphism genotypes and epidemiological data from 49,915 subjects categorised into four phenotypes-metabolically healthy normal weight (MHNW), MUHNW, MHO, and metabolically unhealthy obese (MUHO). We conducted two GWASs using logistic regression analyses and adjustments for confounding variables (model 1: MHNW versus MUHNW and model 2: MHO versus MUHO). GCKR, ABCB11, CDKAL1, LPL, CDKN2B, NT5C2, APOA5, CETP, and APOC1 were associated with metabolically unhealthy phenotypes among normal weight individuals (model 1). LPL, APOA5, and CETP were associated with metabolically unhealthy phenotypes among obese individuals (model 2). The genes common to both models are related to lipid metabolism (LPL, APOA5, and CETP), and those associated with model 1 are related to insulin or glucose metabolism (GCKR, CDKAL1, and CDKN2B). This study reveals the genetic architecture of the MUHNW and MHO phenotypes in a Korean population-based cohort. These findings could help identify individuals at a high metabolic risk in normal weight and obese populations and provide potential novel targets for the management of metabolically unhealthy phenotypes.ope

Identification of Genetic Factors Underlying the Association between Sodium Intake Habits and Hypertension Risk

The role of sodium in hypertension remains unresolved. Although genetic factors have a significant impact on high blood pressure, studies comparing genetic susceptibility between people with low and high sodium diets are lacking. We aimed to investigate the genetic variations related to hypertension according to sodium intake habits in a large Korean population-based study. Data for a total of 57,363 participants in the Korean Genome and Epidemiology Study Health Examination were analyzed. Sodium intake was measured by a semi-quantitative food frequency questionnaire. We classified participants according to sodium intake being less than or greater than 2 g/day. We used logistic regression to test single-marker variants for genetic association with a diagnosis of hypertension, adjusting for age, sex, body mass index, exercise, alcohol, smoking, potassium intake, principal components 1, and principal components 2. Significant associations were defined as p < 5 × 10-8. In participants whose sodium intake was greater than 2 g/day, chromosome 6 open reading frame 10 (C6orf10)-human leukocyte antigen (HLA)-DQB1 rs6913309, ring finger protein (RNF)213 rs112735431, glycosylphosphatidylinositol anchored molecule-like (GML)- cytochrome P450 family 11 subfamily B member 1(CYP11B1) rs3819496, myosin light chain 2 (MYL2)-cut like homeobox 2 (CUX2) rs12229654, and jagged1 (JAG1) rs1887320 were significantly associated with hypertension. In participants whose intake was less than 2 g/day, echinoderm microtubule-associated protein-like 6(EML6) rs67617923 was significantly associated with hypertension. Genetic susceptibility associated with hypertension differed according to sodium intake. Identifying gene variants that contribute to the dependence of hypertension on sodium intake status could make possible more individualized nutritional recommendations for preventing cardiovascular diseases.ope

Comparison of the effectiveness of Martin's equation, Friedewald's equation, and a Novel equation in low-density lipoprotein cholesterol estimation

Low-density-lipoprotein cholesterol (LDL-C) is the main target in atherosclerotic cardiovascular disease (ASCVD). We aimed to validate and compare a new LDL-C estimation equation with other well-known equations. 177,111 samples were analysed from two contemporary population-based cohorts comprising asymptomatic Korean adults who underwent medical examinations. Performances of the Friedewald (FLDL), Martin (MLDL), and Sampson (SLDL) equations in estimating direct LDL-C by homogenous assay were assessed by measures of concordance (R2, RMSE, and mean absolute difference). Analyses were performed according to various triglyceride (TG) and/or LDL-C strata. Secondary analyses were conducted within dyslipidaemia populations of each database. MLDL was superior or at least similar to other equations regardless of TG/LDL-C, in both the general and dyslipidaemia populations (RMSE = 11.45/9.20 mg/dL; R2 = 0.88/0.91; vs FLDL: RMSE = 13.66/10.42 mg/dL; R2 = 0.82/0.89; vs SLDL: RMSE = 12.36/9.39 mg/dL; R2 = 0.85/0.91, per Gangnam Severance Hospital Check-up/Korea Initiatives on Coronary Artery Calcification data). MLDL had a slight advantage over SLDL with the lowest MADs across the full spectrum of TG levels, whether divided into severe hyper/non-hyper to moderate hypertriglyceridaemia samples or stratified by 100-mg/dL TG intervals, even up to TG values of 500-600 mg/dL. MLDL may be a readily adoptable and cost-effective alternative to direct LDL-C measurement, irrespective of dyslipidaemia status. In populations with relatively high prevalence of mild-to-moderate hypertriglyceridaemia, Martin's equation may be optimal for LDL-C and ASCVD risk estimation.ope

Dyslipidemia Risk in Thyroid Cancer Patients: A Nationwide Population-Based Cohort Study

Objective: Thyroid cancer (TC) prevalence has been rapidly increasing. While the relationship between thyroid hormones and lipids has been widely investigated, studies regarding dyslipidemia in patients with TC have been scarce and controversial. We aimed to investigate dyslipidemia risk after TC diagnosis compared to the general population without TC. Method: A population-based prospective study was conducted using data from the Korean National Health Insurance Service-National Sample Cohort Database 2.0 (NHIS-NSC DB 2.0), with health insurance claim data of 1,108,369 subjects between 2002 and 2015. The final study sample comprised 466,735 adult subjects without TC or dyslipidemia diagnoses before the index year, 2009. Bidirectional analyses were performed using prospective and retrospective concepts. In the prospective analysis, Kaplan-Meier estimates were calculated and log-rank tests and univariable and multivariable Cox regression analyses were performed to determine the relationship between TC and dyslipidemia. The retrospective analysis involved 1:5 nested case-control matching based on dyslipidemia status and conditional logistic regression analysis. Results: No significant difference in dyslipidemia incidence was observed between TC patients and the control group, in either the prospective matched (log-rank P = 0.483) or non-matched (log-rank P = 0.424) analyses, or the retrospective analysis (P = 0.3724). In the prospective analysis, 193 patients after TC diagnosis showed similar risk of developing dyslipidemia with the 466,542 controls during the median 7 years of follow-up (unadjusted hazard ratio [HR], 1.102; 95% confidence interval [CI], 0.878-1.383; adjusted HR, 0.932; 95% CI, 0.707-1.230). Multiple propensity score-adjusted models showed similar results, and 114 patients and 570 matched controls showed an HR of 0.818 (95% CI, 0.598-1.120). In the retrospective comparison of dyslipidemia risk in 170 patients and 277,864 controls, the odds ratio was 0.822 (95% CI, 0.534-1.266). Conclusions: Dyslipidemia risk was not significantly different between patients with TC and the general population, in both prospective and retrospective analyses.ope