Corrigendum to "The Association of Body Mass Index and Waist Circumference with the Risk of Achilles Tendon Problems: A Nationwide Population-Based Longitudinal Cohort Study".

[This corrects the article on p. 488 in vol. 15, PMID: 37274500.].

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium.

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

Systematic review on surveillance for non-resected branch-duct intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: The management of branch-duct type intraductal papillary mucinous neoplasms (BD-IPMN) varies in existing guidelines. This study investigated the optimal surveillance protocol and safe discontinuation of surveillance considering natural history in non-resected IPMN, by systematically reviewing the published literature. METHODS: This review was guided by PRISMA. Research questions were framed in PICO format "CQ1-1: Is size criteria helpful to determine surveillance period? CQ1-2: How often should surveillance be carried out? CQ1-3: When should surveillance be discontinued? CQ1-4: Is nomogram predicting malignancy useful during surveillance?". PubMed was searched from January-April 2022. RESULTS: The search generated 2373 citations. After screening, 83 articles were included. Among them, 33 studies were identified for CQ1-1, 19 for CQ1-2, 26 for CQ1-3 and 12 for CQ1-4. Cysts <1.5 or 2 cm without worrisome features (WF) were described as more indolent, and most studies advised an initial period of surveillance. The median growth rate of cysts <2 cm ranged from 0.23 to 0.6 mm/year. Patients with cysts <2 cm showing no morphological changes and no WF after 5-years of surveillance have minimal malignancy risk of 0-2%. Two nomograms created with over 1000 patients had AUCs of around 0.8 and appear to be feasible in a real-world practice. CONCLUSIONS: For patients with suspected BD-IPMN <2 cm and no other WF, less frequent surveillance is recommended. Surveillance may be discontinued for cysts that remain stable during 5-year surveillance, with consideration of patient condition and life expectancy. With this updated surveillance strategy, patients with non-worrisome BD-IPMN should expect more streamlined management and decreased healthcare utilization.

Familial Risk and Interaction With Smoking and Alcohol Consumption in Bladder Cancer: A Population-Based Cohort Study.

Background: Although genetic factors are known to play a role in the pathogenesis of bladder cancer, population-level familial risk estimates are scarce. We aimed to quantify the familial risk of bladder cancer and analyze interactions between family history and smoking or alcohol consumption. Methods: Using the National Health Insurance database, we constructed a cohort of 5,524,403 study subjects with first-degree relatives (FDRs) and their lifestyle risk factors from 2002 to 2019. Familial risk was calculated using hazard ratios (HRs) with 95% confidence intervals (CIs) that compare the risk of individuals with and without affected FDRs. Interactions between family history and smoking or alcohol intake were assessed on an additive scale using the relative excess risk due to interaction (RERI). Results: Offspring with an affected parent had a 2.09-fold (95% CI: 1.41 - 3.08) increased risk of disease compared to those with unaffected parents. Familial risks of those with affected father and mother were 2.26 (95% CI: 1.51 - 3.39) and 1.10 (95% CI: 0.27 - 4.41), respectively. When adjusted for lifestyle factors, HR reduced slightly to 2.04 (95% CI: 1.38 - 3.01), suggesting that a genetic predisposition is the main driver in the familial aggregation. Smokers with a positive family history had a markedly increased risk of disease (HR: 3.60, 95% CI: 2.27 - 5.71), which exceeded the sum of their individual risks, with statistically significant interaction (RERI: 0.72, 95% CI: 0.31 - 1.13). For alcohol consumption, drinkers with a positive family history also had an increased risk of disease, although the interaction was not statistically significant (RERI: 0.05, 95% CI: -3.39 - 3.48). Conclusion: Smokers and alcohol consumers with a positive family history of bladder cancer should be considered a high-risk group and be advised to undergo genetic counseling.

The Association of Body Mass Index and Waist Circumference with the Risk of Achilles Tendon Problems: A Nationwide Population-Based Longitudinal Cohort Study.

Background: The purpose of this study was to evaluate the association of body mass index (BMI) and waist circumference (WC) with the risk of Achilles tendinopathy (AT) or Achilles tendon rupture (ATR), using data from a nationwide population-based cohort. We hypothesized that higher BMI and WC would be independently associated with the increased risk of AT or ATR. In addition, a higher WC may potentiate the association between BMI and the risk of Achilles tendon problems. Methods: We used the National Health Insurance database that covers the entire South Korean population to follow up subjects who participated in the National Health Screening Program (NHSP) from January 2009 to December 2010. The NHSP data include subjects' BMI, WC, blood test results, blood pressure, and information about lifestyle. Among the subjects, those who were newly diagnosed as having AT or ATR before December 31, 2017, were selected. To examine the association of the variables with the risk of AT or ATR and determine whether the effect of higher BMI varied according to WC, multivariate Cox proportional hazards regression was used. Results: Among a total of 16,830,532 subjects, 125,814 and 31,424 developed AT and ATR, respectively. A higher BMI showed a greater association with the increased risk of ATR than AT (adjusted hazard ratio [HR], 3.49 vs. 1.96). A higher WC was associated with the increased risk of AT (adjusted HR, 1.22), but not ATR. In a separate analysis, the association between BMI and the risk of AT was higher when subjects had higher WC as compared to those with lower WC, being most significant in individuals with both higher BMI and higher WC. Conclusions: Higher BMI was more associated with the increased risk of ATR than AT. Moreover, a high central fat distribution played an independent and potentiating role in the development of AT. This implies the greater importance of a high central fat distribution contributing to the development of AT in obese people.

Incidence and Mortality of Vertebral Compression Fracture Among All Age Groups: A Nationwide, Population-based Study in the Republic of Korea.

BACKGROUND: Although several studies have examined the epidemiological features of vertebral compression fractures (VCF) among elderly patients, few studies have reported the epidemiology of VCF among younger individuals. OBJECTIVE: To examine trends in the incidence and mortality of VCF in both the old (>= 65 years) and young (< 65 years) age groups. This study aimed to investigate the incidence and mortality of VCF among all age groups in Korea. STUDY DESIGN: Population-based cohort study. SETTING: A nationwide, population-based setting. METHODS: Using the Korean National Health Insurance database, which has complete population coverage, we identified patients diagnosed with VCF between 2005 to 2018. Differences in incidence, survival and mortality were compared across groups using Kaplan-Meier analysis and Cox regression for all age groups and both genders. RESULTS: We identified a total of 742,993 VCF patients and the annual incidence was 140.09/100,000 individuals. Although the incidence of VCF was significantly higher in the older age compared to younger age group (556.38/100,000 vs. 44.09/100,000 individuals), the mortality rate ratio for VCF patients was higher among younger compared to older individuals (old: 1.59 vs. young: 2.87). In our multivariable-adjusted analysis, the hazard ratio for multiple fractures, traumatic injury and osteoporosis were higher in patients aged < 65 years compared to patients aged >= 65 years, suggesting that the impact of these clinical variables on mortality is more significant in the younger age group. LIMITATION: A limitation of this study was its lack of information on clinical features, such as disease severity and laboratory data. The precise cause of death of VCF patients could not be confirmed from the study database. CONCLUSIONS: The mortality rate ratio and hazard ratio were significantly higher among younger patients with VCF, indicating the need for further research on VCF in younger age groups.

Familial Risk of Graves Disease Among First-Degree Relatives and Interaction With Smoking: A Population-Based Study.

CONTEXT: Population-based studies on the familial aggregation of Graves disease (GD) are scarce and gene-environment interactions are not well-studied. OBJECTIVE: We evaluated the familial aggregation of GD and assessed interactions between family history and smoking. METHODS: Using the National Health Insurance database, which includes information on familial relationships and lifestyle risk factors, we identified 5 524 403 individuals with first-degree relatives (FDRs). Familial risk was calculated using hazard ratios (HRs), comparing the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using relative excess risk due to interaction (RERI). RESULTS: The HR among individuals with affected FDRs was 3.39 (95% CI, 3.30-3.48) compared with those without affected FDR, and among individuals with affected twin, brother, sister, father, and mother, the HRs were 36.53 (23.85-53.54), 5.26 (4.89-5.66), 4.12 (3.88-4.38), 3.34 (3.16-3.54), and 2.63 (2.53-2.74), respectively. Individuals with both a positive family history and smoking had an increased risk of disease (HR 4.68) with statistically significant interaction (RERI 0.94; 95% CI, 0.74-1.19). Heavy smokers with a positive family history showed a nearly 6-fold increased risk, which was higher than moderate smoking, suggesting a dose-response interaction pattern. Current smoking also showed a statistically significant interaction with family history (RERI 0.52; 95% CI, 0.22-0.82), while this was not observed for former smoking. CONCLUSION: A gene-environment interaction can be suggested between smoking and GD-associated genetic factors, which diminishes after smoking cessation. Smokers with a positive family history should be considered a high-risk group and smoking cessation should be advised.

Familial risk of seropositive rheumatoid arthritis and interaction with smoking: a population-based cohort study.

OBJECTIVES: We evaluated the familial risk of seropositive rheumatoid arthritis (RA) and examined interactions between family history and smoking. METHODS: Using the National Health Insurance and Health Screening Program databases, which include information on familial relationships and lifestyle factors, we identified 5 524 403 individuals with first-degree relatives (FDRs) from 2002-2018. We calculated familial risk using hazard ratios (HRs) with 95% CIs which compare the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using the relative excess risk due to interaction (RERI). RESULTS: Individuals with affected FDR had 4.52-fold (95% CI 3.98, 5.12) increased risk of disease compared with those with unaffected FDR. Familial risk adjusted for lifestyle factors decreased slightly (HR 4.49), suggesting that a genetic contribution is the predominant driver in the familial aggregation of RA. Smoking was associated with an increased risk of disease that was more pronounced among heavy (HR 1.92 95% CI 1.70, 2.18) compared with moderate (HR 1.15 95% CI 1.04, 1.28) smoking. In the interaction analysis, the risk associated with the combined effect of smoking and family history was higher than the sum of their individual effects, though statistically non-significant (RERI 1.30 95% CI ‒0.92, 3.51). Heavy smokers with a positive family history showed a prominent interaction (RERI 4.13 95% CI ‒0.88, 9.13) which exceeded moderate smokers (RERI 0.61 95% CI ‒1.90, 3.13), suggesting a dose-response interaction pattern. CONCLUSION: Our findings indicate the possibility of an interaction between RA-associated genes and smoking.

Familial Risk of Gout and Interaction With Obesity and Alcohol Consumption: A Population-Based Cohort Study in Korea.

OBJECTIVE: Population-based studies of the familial aggregation of gout are scarce, and gene/environment interactions are not well studied. This study was undertaken to evaluate the familial aggregation of gout as well as assess interactions between family history and obesity or alcohol consumption on the development of gout. METHODS: Using the Korean National Health Insurance database, which includes information regarding familial relationships and risk factor data, we identified 5,524,403 individuals from 2002 to 2018. Familial risk was calculated using hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare the risk in individuals with and those without affected first-degree relatives. Interactions between family history and obesity/alcohol consumption were assessed on an additive scale using the relative excess risk due to interaction (RERI). RESULTS: Individuals with a gout-affected first-degree relative had a 2.42-fold (95% CI 2.39, 2.46) increased risk of disease compared to those with unaffected first-degree relatives. Having both a family history of gout and being either overweight or having moderate alcohol consumption was associated with a markedly increased risk of disease, with HRs of 4.39 (95% CI 4.29, 4.49) and 2.28 (95% CI 2.22, 2.35), respectively, which exceeded the sum of their individual risks but was only statistically significant in overweight individuals (RERI 0.96 [95% CI 0.85, 1.06]). Obese individuals (RERI 1.88 [95% CI 1.61, 2.16]) and heavy drinkers (RERI 0.36 [95% CI 0.20, 0.52]) had a more prominent interaction compared to overweight individuals and moderate drinkers, suggesting a dose-response interaction pattern. CONCLUSION: Our findings indicate the possibility of an interaction between gout-associated genetic factors and obesity/alcohol consumption.

Descriptive Analysis of Gastric Cancer Mortality in Korea, 2000-2020.

PURPOSE: This study aimed to examine secular trends, age-period-cohort effects, and geographical differences in gastric cancer (GC) mortality in Korea. Materials and Methods: Using cause of death data from the Korean Statistical Information Service for GC from 2000 to 2020, we calculated average annual percentage changes (AAPCs) in the age-standardized mortality of GC in 17 cities and provinces through joinpoint regression. Decomposition of age, period, and cohort effects on GC mortality were elucidated by applying a log-linear model and an intrinsic estimate method. Spatial patterns and the degree of spatial clustering in 250 administrative regions were explored via Moran's I statistics. Stratification by sex was performed for all analyses. RESULTS: The age-standardized mortality of GC per 100,000 persons declined from 29.0 in 2000 to 7.9 in 2020 (AAPC, -6.28%). Age-period-cohort analyses of GC mortality showed a downward trend among five-year age groups from age 20-89 years across five-year periods from 2005-2020 and five-year birth cohorts from 1920-2000. Overall, the younger birth cohort showed lower mortality rates than the older cohort within the same period. In 2020, clusters of high GC mortality were observed in the central area for men (Chungcheongbuk, Jeollabuk, Gyeongsangbuk, and Gyeongsangnam) and in the eastern area for women (Gyeongsangbuk). CONCLUSION: This study identified a downward trend in GC mortality among men and women from 2000 to 2020 in Korea. This trend was mainly attributed to birth cohort rather than period effects. Spatial analysis showed high GC mortality in the Chungcheong and Gyeongsangbuk areas.

Familial Risk of Renal Cell Cancer and Interaction with Obesity and Hyperglycemia: A Population-Based Study.

PURPOSE: We quantified the familial risk of renal cell cancer (RCC) among first-degree relatives (FDRs) on a population level, and examined interactions between family history and body mass index or blood glucose. MATERIALS AND METHODS: Using the National Health Insurance database, which covers the entire Korean population, and the National Health Screening Program, we constructed a cohort of 5,524,403 individuals with blood-related FDRs and their lifestyle factors from 2002 to 2018. We calculated familial risk using incidence risk ratios (IRRs) with 95% confidence intervals, which compares the risk of individuals with and without FDR. The combined effect and interaction of a given risk factor and family history of RCC were measured by the relative excess risk due to interaction. RESULTS: Individuals with affected FDRs showed a 2.29-fold (95% CI 1.68-3.13) increased risk of disease. Familial risk adjusted for lifestyle factors showed minimal attenuation (IRR 2.25; 95% CI: 1.65-3.08), suggesting that genetic predisposition is the main contributor in the familial aggregation of RCC. Individuals with both a positive family history and overweight/obesity (IRR 3.71, 95% CI 2.50-4.92) or hyperglycemia (IRR 4.52, 95% CI 2.59-6.45) had a significantly higher risk that exceeded the sum of their individual risks, suggesting an interaction that was statistically significant (relative excess risk due to interaction 95% CI: 0.91, -0.21-2.12; 2.21, 0.28-4.14). CONCLUSIONS: Our findings suggest an interaction between genetic and environmental factors, namely obesity and hyperglycemia. Individuals with both factors should be considered a high-risk group and advised to undergo genetic counseling.

Familial Risk and Its Interaction With Body Mass Index and Physical Activity in Anterior Cruciate Ligament Injury Among First-Degree Relatives: A Population-Based Cohort Study.

BACKGROUND: Genetic and behavioral risk factors have been suggested to play a role in anterior cruciate ligament (ACL) injury. However, population-based familial risk estimates are unavailable. PURPOSE: To quantify familial risk of ACL injury among first-degree relatives (FDRs) after controlling for certain behavioral risk factors. To estimate the combined effect of family history and body mass index (BMI) or physical activity on the risk of ACL injury. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Using nationwide data from the Korean National Health Insurance and National Health Screening Program databases on kinship, lifestyle habits, and anthropometrics, 5,184,603 individuals with blood-related FDRs were identified from 2002 to 2018. Familial risk of ACL injury, as represented as incidence risk ratios (IRRs) with 95% CIs, was analyzed using Cox proportional hazards models among individuals with versus without affected FDRs. Analyses were adjusted for age, sex, and behavioral risk factors. Interaction testing between familial history and BMI or physical activity was performed on an additive scale. RESULTS: The risk of ACL injury was 1.79-fold higher (IRR, 1.79; 95% CI, 1.73-1.85) among individuals with versus without affected FDRs, and the incidence was 12.61 per 10,000 person-years. The IRR (95% CI) was highest with affected twins at 4.49 (3.01-6.69), followed by siblings at 2.31 (2.19-2.44), the father at 1.58 (1.49-1.68), and the mother at 1.52 (1.44-1.61). High BMI and high level of physical activity were significantly associated with the risk of ACL injury. Individuals with positive family history and either high BMI or physical activity had a 2.59- and 2.45-fold increased risk of injury as compared with the general population, respectively, and the combined risks exceeded the sum of their independent risks. CONCLUSION: Familial factors are risk factors for ACL injury with an additional contribution of 2 behavioral factors: BMI and physical activity level. A significant interaction was observed between family history of ACL injury and high BMI/level of physical activity.

Familial Risk of Hashimoto's Thyroiditis Among First-Degree Relatives: A Population-Based Study in Korea.

Background: Few small-scale studies have reported a genetic and familial predisposition in Hashimoto's thyroiditis (HT), however, quantified familial risk estimates from population-level data are unavailable. We aimed to estimate the incidence and familial risk of HT among first-degree relatives (FDR) according to age, sex, and family relationships. Methods: We conducted a population-based study in the general population of Korea from 2002 to 2017. Using the nationwide health insurance database, which has full population coverage and family relationship information, a cohort of 22 million individuals with blood-related FDR comprising 12 million families were followed up for a familial occurrence of HT. Age- and sex-adjusted incidence risk ratios (IRRs) were calculated in individuals with an affected FDR compared with those without an affected FDR. Results: Among 21,940,795 individuals, 234,912 had an HT-affected FDR, of whom 2425 familial cases developed HT with an incidence of 7.12/10,000 person-years. The familial risk for HT was 6.5-fold (95% confidence interval [CI]: 6.24-6.78) higher in individuals with versus without affected FDR. According to relationship, familial risks were IRR 102.71, IRR 7.80, IRR 5.54, and IRR 5.52 with an affected twin, sibling, mother, and father, respectively, and the corresponding incidence (/10,000 person-years) was 115.57, 10.66, 5.73, and 5.91. Same-sex twins had three times higher risk of developing HT than opposite-sex twins (IRR 121.01 vs. 21.46). The sex-specific familial risk was higher in males than females. The risks demonstrated age dependence, being higher in younger age groups. Conclusions: This study represents the largest population-based study of familial HT risk in Asia. We demonstrated elevated familial risk of incident HT among FDR, but with lower magnitude as those observed in previous studies. Familial risk increased with the degree of genetic relatedness among FDR indicating a prominent role of genetic factors in the familial aggregation of HT. Elevated risks in the younger age groups should motivate clinicians to screen people with a family history, especially those <30 years.

Significant Decline in the Incidence of Behçet's Disease in South Korea: A Nationwide Population-Based Study (2004-2017).

OBJECTIVE: Long-term population-based data on change in the incidence of Behçet's disease (BD) are scarce, although a possible decline has been reported. The present study was undertaken to investigate the incidence, survival, and mortality of BD patients from 2004 to 2017 in the Republic of Korea. METHODS: We analyzed a registry of rare intractable diseases and a claims database from the Health Insurance and Review Agency with information on BD patients between 2004 and 2017 using uniform diagnostic criteria. The study period was divided into 3 time periods: 2004-2006, 2007-2010, and 2011-2017. RESULTS: The annual incidence of BD decreased from 8.15 per 100,000 in 2004 to 1.51 in 2017, an 81.5% decrease. The annual percentage change was 6.32% for female patients and 6.15% for male patients. The decrease in BD incidence was greater for women and middle-aged people. The 3-year survival rate of BD patients during the 2011-2017 period was lower than that of BD patients in 2004-2006 and 2007-2010, although there was no statistical difference. The standardized mortality rates increased significantly in the 2011-2017 period compared to the first 2 periods. CONCLUSION: BD incidence decreased from 2004 to 2017 in the Republic of Korea. This decline in incidence might be attributable to changes in environmental factors, including a reduction in the burden of infectious diseases in the past decades and improvement in oral health during childhood. The unprecedented decline in the incidence of BD in the Republic of Korea without major changes in genetic background suggests that environmental factors are very important to the development of BD.

Familial risk of Behçet's disease among first-degree relatives: a population-based aggregation study in Korea.

OBJECTIVE: Previous studies have indicated that Behçet's disease (BD) has a genetic component, however population-level familial risk estimates are unavailable. We quantified the familial incidence and risk of BD in first-degree relatives (FDR) according to age, sex and type of family relationship. METHODS: Using the Korean National Health Insurance database, which has full population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 individuals comprising 12 million families, which were followed for a familial occurrence of BD from 2002 to 2017. Age- and sex-adjusted incidence risk ratios for BD were calculated in individuals with affected FDR compared with those without affected FDR. RESULTS: Among the total study population, 53 687 individuals had affected FDR, of whom 284 familial cases developed BD with an incidence of 3.57/104 person-years. The familial risk (incidence) for BD was increased to 13.1-fold (2.71/104 person-years) in individuals with an affected father, 13.9-fold (3.11/104 person-years) with affected mother, 15.2-fold (4.9/104 person-years) with an affected sibling and the highest risk was 165-fold (46/104 person-years) with an affected twin. Familial risks showed age dependence, being higher in younger age groups. The sex-specific familial risk was similar in males and females. CONCLUSION: This study provides quantified estimates of familial incidence and risk in FDR of BD patients in an entire population. Familial risks were higher within generation (sibling-sibling) vs between generations (parent-offspring). This implicates complex interactions between genetic factors and shared childhood environmental exposures in the pathogenesis of BD.

Familial Risk of Inflammatory Bowel Disease: A Population-Based Cohort Study in South Korea.

BACKGROUND & AIMS: Despite the rapid increase in inflammatory bowel disease (IBD), population-level familial risk estimates of IBDs still are lacking in Asian-Pacific countries. We aimed to quantify the familial risk of incident IBD among first-degree relatives (FDRs) of individuals with IBD according to age, sex, and familial relationship. METHODS: Using the South Korea National Health Insurance database (2002-2017), which has complete population coverage and confirmed accuracy of both FDR information and IBD diagnoses, we constructed a cohort of 21,940,795 study subjects comprising 12 million distinct families. We calculated incidence risk ratios of ulcerative colitis (UC) or Crohn's disease (CD) in individuals of affected FDRs compared with individuals without affected FDRs. RESULTS: Of 45,717 individuals with UC and 17,848 individuals with CD, 3.8% and 3.1% represented familial cases, respectively. Overall, there was a 10.2-fold (95% CI, 9.39-11.1) and a 22.1-fold (95% CI, 20.5-24.5) significantly higher adjusted risk of UC and CD among FDRs of individuals with vs without IBD. Familial risk was highest among twins, followed by nontwin siblings, and then offspring of affected parents. Familial risk generally was higher within generations (sibling-sibling) vs between generations (parent-offspring). Familial risk also increased with the increasing number of affected FDRs. CONCLUSIONS: According to this population-based analysis, there is a substantially increased risk of IBD among FDRs of affected individuals, with the highest risk among siblings and for CD. These findings might help with an earlier diagnosis and appropriate therapeutic intervention in FDRs of individuals with IBD. Dedicated studies are needed to evaluate the contributions of shared early-in-life environmental exposures and genetic factors.

Familial Risk for Moyamoya Disease Among First-Degree Relatives, Based on a Population-Based Aggregation Study in Korea.

BACKGROUND AND PURPOSE: Genetic factors have been known to play a role in the etiology of moyamoya disease (MMD); however, population-level studies quantifying familial risk estimates are unavailable. We aimed to quantify familial incidence and risk for MMD in first-degree relatives (FDR) in the general population of Korea. METHODS: By using the Korean National Health Insurance database which has complete population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 study subjects constituting 12 million families with blood-related FDR and followed them for a familial occurrence of MMD from 2002 to 2017. Incidence risk ratios were calculated as MMD incidence in individuals with affected FDR compared with those without affected FDR, according to age, sex, and family relationships. RESULTS: Among total study subjects, there were 22 459 individuals with affected FDR, of whom 712 familial cases developed MMD with an incidence of 21.8/104 person-years. Overall, the familial risk for MMD was 132-fold higher in individuals with versus without affected FDR. Familial risk (incidence risk ratio; incidence/104 person-years) increased with the degree of genetic relatedness, being highest in individuals with an affected twin (1254.1; 230.0), followed by a sibling (212.4; 35.6), then mother (87.7; 14.4) and father (62.5; 10.4). Remarkably, there was no disease concordance between spouses. The risks were age-dependent and were particularly high in younger age groups. Familial risks were similar in males and females, and the risk of disease transmission was higher in same-sex parent-offspring and sibling pairs. CONCLUSIONS: Our study indicates that genetic predisposition is the predominant driver in MMD pathogenesis, with minimal contribution of environmental factors. These results could be utilized to direct future genetic studies and clinical risk counseling.