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Among Asian-Pacific populations, the first-degree relatives (FDRs) of individuals with inflammatory bowel disease (IBD) have a significantly increased risk for IBD themselves, according to a large analysis of data from South Korea. The greatest risk was found in siblings and for Crohn’s disease (CD).
The analysis of the South Korean Health Insurance Database included a cohort of 21,940,795 individuals from about 12 million families, with data collected between 2002 and 2017.
Previous studies have examined risk of IBD and familial relationships with existing IBD patients, but they have been subject to biases and have been heterogeneous in design, according to the authors, led by co–first authors Hyun Jung Kim, MD, of Korea University in Seoul, South Korea, and Shailja C. Shah, MD, of Vanderbilt University in Nashville, Tenn. There are few true population-based studies that quantify specific risks for family members of IBD patients, and none that were conducted in non-Western populations.
There are concerns about extrapolating familial IBD risk estimates from Western European populations to Asian populations because new data suggest that there are both genetic and nongenetic disease risk factors that reflect geography and ethnicity, the authors noted.
The researchers identified 45,717 individuals with ulcerative colitis (UC) and 17,848 with CD. Mean annual incidence rates were 4.6 cases of UC and 3.2 cases of CD per 100,000 person-years, which was relatively stable across the study period.
In all, 3.8% of UC and 3.1% of CD diagnoses occurred in FDR’s of existing patients. Among those with an FDR with IBD, the incidence of UC and CD was 54.5 and 99.2 per 100,000 person-years, respectively. When compared with individuals who had no FDRs with IBD, subjects who had an FDR with CD were at a more than 20-fold increased risk of CD (incident rate ratio, 22.2; 95% confidence interval, 20.5-24.5), whereas individuals with an FDR with UC were at a little more than a 10-fold risk for UC (IRR, 10.2; 95% CI, 9.39-11.1).
Subjects with an FDR with CD were at higher risk of UC (IRR, 3.56; 95% CI, 2.77-4.50), and those with an FDR with UC were at higher risk of CD (IRR, 2.94; 95% CI, 2.45-3.49). After adjustment for smoking, having an FDR with IBD was associated with an almost eightfold increased risk of UC (IRR, 7.94; 95% CI, 6.98-9.03) and a nearly 20-fold increased risk of CD (IRR, 19.03; 95% CI, 15.58-23.25).
The investigators also performed an analysis based on type of relative, with matching relations with unaffected relatives as the reference for each comparison. The highest risk for incident CD was with twin siblings (IRR, 336.2; 95% CI, 235.0-481.1) followed by nontwin siblings (IRR, 27.6; 95% CI, 24.6-30.9). The risk of CD among offspring of an affected father was 9.40 (95% CI, 6.81-13.0) and 6.54 (95% CI, 4.17-10.3) for offspring of affected mothers. There was a similar pattern for UC, although the magnitude was smaller: 163.7 for twin siblings (95% CI, 105.6-253.9), 13.1 for nontwin siblings (95% CI, 11.4-15.0), 7.11 for offspring of affected fathers (95% CI, 6.10-8.29), and 8.77 for offspring of affected mothers (95% CI, 7.46-10.3).
The researchers found no evidence of a birth cohort effect. Family history and IBD risk is a complicated relationship. Family history includes shared genetics as well as similar environmental exposures, and gene-environment interactions can add another layer of uncertainty. Previous studies have found that asymptomatic family members of IBD patients sometimes have preclinical signs such as changes in intestinal permeability, immune function, the microbiome, and biomarker levels.
IBD has emerged recently among Asian-Pacific populations as a serious health concern, with a recent rapid increase. This may reflect a shift in potentially modifiable environmental triggers. “Precisely quantifying familial risk and patterns might enable more accurate risk counseling and better-targeted clinical surveillance for earlier diagnosis and treatment among FDRs. Moreover, an accurate definition of familial IBD risk across populations also might inform subsequent investigations untangling the various shared environmental and genetic contributions,” the authors wrote.
Although genetic susceptibility is generally accepted as the predominant driver in familial trends for IBD, the authors noted their “study was not designed to determine the contribution of genetic vs. nongenetic determinants to familial IBD risk, and future well-designed dedicated investigations are needed to provide this clarity.”
The study is limited by the relatively short follow-up period, which may not have captured all IBD cases within patients’ families.
The authors have no relevant financial disclosures.
One of the hallmarks of effective IBD management is early disease intervention to modify the natural history. This work will be instrumental in counseling patients’ families on the need to monitor for subclinical red flag or early warning signs, and it will be important to recognize that male and female IBD patients will both need to be counseled equally on the risk of offspring developing IBD. Further work will be needed to understand whether modifiable risk factors can be identified to help prevent the development of IBD in these at-risk individuals and whether specific mutations are responsible for multilineage IBD syndromes affecting several generations or multiple first-degree relatives.
Parambir S. Dulai, MD, is an assistant professor in the division of gastroenterology and hepatology at University of California, San Diego. He has no relevant conflicts of interest.
One of the hallmarks of effective IBD management is early disease intervention to modify the natural history. This work will be instrumental in counseling patients’ families on the need to monitor for subclinical red flag or early warning signs, and it will be important to recognize that male and female IBD patients will both need to be counseled equally on the risk of offspring developing IBD. Further work will be needed to understand whether modifiable risk factors can be identified to help prevent the development of IBD in these at-risk individuals and whether specific mutations are responsible for multilineage IBD syndromes affecting several generations or multiple first-degree relatives.
Parambir S. Dulai, MD, is an assistant professor in the division of gastroenterology and hepatology at University of California, San Diego. He has no relevant conflicts of interest.
One of the hallmarks of effective IBD management is early disease intervention to modify the natural history. This work will be instrumental in counseling patients’ families on the need to monitor for subclinical red flag or early warning signs, and it will be important to recognize that male and female IBD patients will both need to be counseled equally on the risk of offspring developing IBD. Further work will be needed to understand whether modifiable risk factors can be identified to help prevent the development of IBD in these at-risk individuals and whether specific mutations are responsible for multilineage IBD syndromes affecting several generations or multiple first-degree relatives.
Parambir S. Dulai, MD, is an assistant professor in the division of gastroenterology and hepatology at University of California, San Diego. He has no relevant conflicts of interest.
Among Asian-Pacific populations, the first-degree relatives (FDRs) of individuals with inflammatory bowel disease (IBD) have a significantly increased risk for IBD themselves, according to a large analysis of data from South Korea. The greatest risk was found in siblings and for Crohn’s disease (CD).
The analysis of the South Korean Health Insurance Database included a cohort of 21,940,795 individuals from about 12 million families, with data collected between 2002 and 2017.
Previous studies have examined risk of IBD and familial relationships with existing IBD patients, but they have been subject to biases and have been heterogeneous in design, according to the authors, led by co–first authors Hyun Jung Kim, MD, of Korea University in Seoul, South Korea, and Shailja C. Shah, MD, of Vanderbilt University in Nashville, Tenn. There are few true population-based studies that quantify specific risks for family members of IBD patients, and none that were conducted in non-Western populations.
There are concerns about extrapolating familial IBD risk estimates from Western European populations to Asian populations because new data suggest that there are both genetic and nongenetic disease risk factors that reflect geography and ethnicity, the authors noted.
The researchers identified 45,717 individuals with ulcerative colitis (UC) and 17,848 with CD. Mean annual incidence rates were 4.6 cases of UC and 3.2 cases of CD per 100,000 person-years, which was relatively stable across the study period.
In all, 3.8% of UC and 3.1% of CD diagnoses occurred in FDR’s of existing patients. Among those with an FDR with IBD, the incidence of UC and CD was 54.5 and 99.2 per 100,000 person-years, respectively. When compared with individuals who had no FDRs with IBD, subjects who had an FDR with CD were at a more than 20-fold increased risk of CD (incident rate ratio, 22.2; 95% confidence interval, 20.5-24.5), whereas individuals with an FDR with UC were at a little more than a 10-fold risk for UC (IRR, 10.2; 95% CI, 9.39-11.1).
Subjects with an FDR with CD were at higher risk of UC (IRR, 3.56; 95% CI, 2.77-4.50), and those with an FDR with UC were at higher risk of CD (IRR, 2.94; 95% CI, 2.45-3.49). After adjustment for smoking, having an FDR with IBD was associated with an almost eightfold increased risk of UC (IRR, 7.94; 95% CI, 6.98-9.03) and a nearly 20-fold increased risk of CD (IRR, 19.03; 95% CI, 15.58-23.25).
The investigators also performed an analysis based on type of relative, with matching relations with unaffected relatives as the reference for each comparison. The highest risk for incident CD was with twin siblings (IRR, 336.2; 95% CI, 235.0-481.1) followed by nontwin siblings (IRR, 27.6; 95% CI, 24.6-30.9). The risk of CD among offspring of an affected father was 9.40 (95% CI, 6.81-13.0) and 6.54 (95% CI, 4.17-10.3) for offspring of affected mothers. There was a similar pattern for UC, although the magnitude was smaller: 163.7 for twin siblings (95% CI, 105.6-253.9), 13.1 for nontwin siblings (95% CI, 11.4-15.0), 7.11 for offspring of affected fathers (95% CI, 6.10-8.29), and 8.77 for offspring of affected mothers (95% CI, 7.46-10.3).
The researchers found no evidence of a birth cohort effect. Family history and IBD risk is a complicated relationship. Family history includes shared genetics as well as similar environmental exposures, and gene-environment interactions can add another layer of uncertainty. Previous studies have found that asymptomatic family members of IBD patients sometimes have preclinical signs such as changes in intestinal permeability, immune function, the microbiome, and biomarker levels.
IBD has emerged recently among Asian-Pacific populations as a serious health concern, with a recent rapid increase. This may reflect a shift in potentially modifiable environmental triggers. “Precisely quantifying familial risk and patterns might enable more accurate risk counseling and better-targeted clinical surveillance for earlier diagnosis and treatment among FDRs. Moreover, an accurate definition of familial IBD risk across populations also might inform subsequent investigations untangling the various shared environmental and genetic contributions,” the authors wrote.
Although genetic susceptibility is generally accepted as the predominant driver in familial trends for IBD, the authors noted their “study was not designed to determine the contribution of genetic vs. nongenetic determinants to familial IBD risk, and future well-designed dedicated investigations are needed to provide this clarity.”
The study is limited by the relatively short follow-up period, which may not have captured all IBD cases within patients’ families.
The authors have no relevant financial disclosures.
Among Asian-Pacific populations, the first-degree relatives (FDRs) of individuals with inflammatory bowel disease (IBD) have a significantly increased risk for IBD themselves, according to a large analysis of data from South Korea. The greatest risk was found in siblings and for Crohn’s disease (CD).
The analysis of the South Korean Health Insurance Database included a cohort of 21,940,795 individuals from about 12 million families, with data collected between 2002 and 2017.
Previous studies have examined risk of IBD and familial relationships with existing IBD patients, but they have been subject to biases and have been heterogeneous in design, according to the authors, led by co–first authors Hyun Jung Kim, MD, of Korea University in Seoul, South Korea, and Shailja C. Shah, MD, of Vanderbilt University in Nashville, Tenn. There are few true population-based studies that quantify specific risks for family members of IBD patients, and none that were conducted in non-Western populations.
There are concerns about extrapolating familial IBD risk estimates from Western European populations to Asian populations because new data suggest that there are both genetic and nongenetic disease risk factors that reflect geography and ethnicity, the authors noted.
The researchers identified 45,717 individuals with ulcerative colitis (UC) and 17,848 with CD. Mean annual incidence rates were 4.6 cases of UC and 3.2 cases of CD per 100,000 person-years, which was relatively stable across the study period.
In all, 3.8% of UC and 3.1% of CD diagnoses occurred in FDR’s of existing patients. Among those with an FDR with IBD, the incidence of UC and CD was 54.5 and 99.2 per 100,000 person-years, respectively. When compared with individuals who had no FDRs with IBD, subjects who had an FDR with CD were at a more than 20-fold increased risk of CD (incident rate ratio, 22.2; 95% confidence interval, 20.5-24.5), whereas individuals with an FDR with UC were at a little more than a 10-fold risk for UC (IRR, 10.2; 95% CI, 9.39-11.1).
Subjects with an FDR with CD were at higher risk of UC (IRR, 3.56; 95% CI, 2.77-4.50), and those with an FDR with UC were at higher risk of CD (IRR, 2.94; 95% CI, 2.45-3.49). After adjustment for smoking, having an FDR with IBD was associated with an almost eightfold increased risk of UC (IRR, 7.94; 95% CI, 6.98-9.03) and a nearly 20-fold increased risk of CD (IRR, 19.03; 95% CI, 15.58-23.25).
The investigators also performed an analysis based on type of relative, with matching relations with unaffected relatives as the reference for each comparison. The highest risk for incident CD was with twin siblings (IRR, 336.2; 95% CI, 235.0-481.1) followed by nontwin siblings (IRR, 27.6; 95% CI, 24.6-30.9). The risk of CD among offspring of an affected father was 9.40 (95% CI, 6.81-13.0) and 6.54 (95% CI, 4.17-10.3) for offspring of affected mothers. There was a similar pattern for UC, although the magnitude was smaller: 163.7 for twin siblings (95% CI, 105.6-253.9), 13.1 for nontwin siblings (95% CI, 11.4-15.0), 7.11 for offspring of affected fathers (95% CI, 6.10-8.29), and 8.77 for offspring of affected mothers (95% CI, 7.46-10.3).
The researchers found no evidence of a birth cohort effect. Family history and IBD risk is a complicated relationship. Family history includes shared genetics as well as similar environmental exposures, and gene-environment interactions can add another layer of uncertainty. Previous studies have found that asymptomatic family members of IBD patients sometimes have preclinical signs such as changes in intestinal permeability, immune function, the microbiome, and biomarker levels.
IBD has emerged recently among Asian-Pacific populations as a serious health concern, with a recent rapid increase. This may reflect a shift in potentially modifiable environmental triggers. “Precisely quantifying familial risk and patterns might enable more accurate risk counseling and better-targeted clinical surveillance for earlier diagnosis and treatment among FDRs. Moreover, an accurate definition of familial IBD risk across populations also might inform subsequent investigations untangling the various shared environmental and genetic contributions,” the authors wrote.
Although genetic susceptibility is generally accepted as the predominant driver in familial trends for IBD, the authors noted their “study was not designed to determine the contribution of genetic vs. nongenetic determinants to familial IBD risk, and future well-designed dedicated investigations are needed to provide this clarity.”
The study is limited by the relatively short follow-up period, which may not have captured all IBD cases within patients’ families.
The authors have no relevant financial disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY