Gallstones

Genetics versus environment

Attila Nakeeb, Anthony G. Comuzzie, Lisa Martin, Gabriele E. Sonnenberg, Debra Swartz-Basile, Ahmed H. Kissebah, Henry A. Pitt

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Objective: The aim of this study was to determine if a significant genetic component contributes to the pathogenesis of symptomatic gallstones. Summary Background Data: Gallstones represent a polygenic disorder that affects more than 30,000,000 Americans and results in more than 750,000 cholecystectomies in the United States annually. Risk factors include age, gender, race, parity, obesity, and diabetes. A family history of gallstones also has been identified as a risk factor suggesting that genetics play a role in gallstone formation. However, the role of genetics in the pathogenesis of gallstone formation has not been determined. Methods: A gallbladder disease-specific questionnaire was administered to 904 healthy unrelated adult volunteers (association study). The questionnaire ascertained a history of cholecystectomy and gallstone disease in first-degree relatives, as well as medical history, demographic, and anthropometric data. A logistic regression model was used to identify risk factors for symptomatic gallstone disease in a multivariate analysis. A maximum likelihood based variance decomposition approach was then used in 1,038 individuals from 358 families (family study) to estimate the additive genetic heritability of symptomatic gallstone disease. Results: In the association study significant risk factors for symptomatic gallstone disease were female gender (relative risk 8.8, P <.003), obesity (BMI > 30, relative risk 3.7, P <.001), age > 50 (relative risk 2.5, P <.001), and a positive family history of previous cholecystectomy in a first-degree family member (relative risk 2.2, P <.01). In the family study the additive genetic heritability of symptomatic gallstones was 29% (P <.02), age and gender were significant covariates and explained 9.3% of the phenotypic variation in gallbladder disease. Conclusions: These data suggest that genetic factors are responsible for at least 30% of symptomatic gallstone disease. However, the true role of heredity in gallstone pathogenesis is probably higher because data based on symptomatic gallbladder disease underestimates the true prevalence in the population.

Original languageEnglish (US)
Pages (from-to)842-849
Number of pages8
JournalAnnals of Surgery
Volume235
Issue number6
DOIs
StatePublished - 2002
Externally publishedYes

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Gallstones
Gallbladder Diseases
Cholecystectomy
Logistic Models
Heredity
Parity
Volunteers
Multivariate Analysis
Obesity
Demography

ASJC Scopus subject areas

  • Surgery

Cite this

Nakeeb, A., Comuzzie, A. G., Martin, L., Sonnenberg, G. E., Swartz-Basile, D., Kissebah, A. H., & Pitt, H. A. (2002). Gallstones: Genetics versus environment. Annals of Surgery, 235(6), 842-849. https://doi.org/10.1097/00000658-200206000-00012

Gallstones : Genetics versus environment. / Nakeeb, Attila; Comuzzie, Anthony G.; Martin, Lisa; Sonnenberg, Gabriele E.; Swartz-Basile, Debra; Kissebah, Ahmed H.; Pitt, Henry A.

In: Annals of Surgery, Vol. 235, No. 6, 2002, p. 842-849.

Research output: Contribution to journalArticle

Nakeeb, A, Comuzzie, AG, Martin, L, Sonnenberg, GE, Swartz-Basile, D, Kissebah, AH & Pitt, HA 2002, 'Gallstones: Genetics versus environment', Annals of Surgery, vol. 235, no. 6, pp. 842-849. https://doi.org/10.1097/00000658-200206000-00012
Nakeeb A, Comuzzie AG, Martin L, Sonnenberg GE, Swartz-Basile D, Kissebah AH et al. Gallstones: Genetics versus environment. Annals of Surgery. 2002;235(6):842-849. https://doi.org/10.1097/00000658-200206000-00012
Nakeeb, Attila ; Comuzzie, Anthony G. ; Martin, Lisa ; Sonnenberg, Gabriele E. ; Swartz-Basile, Debra ; Kissebah, Ahmed H. ; Pitt, Henry A. / Gallstones : Genetics versus environment. In: Annals of Surgery. 2002 ; Vol. 235, No. 6. pp. 842-849.
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AB - Objective: The aim of this study was to determine if a significant genetic component contributes to the pathogenesis of symptomatic gallstones. Summary Background Data: Gallstones represent a polygenic disorder that affects more than 30,000,000 Americans and results in more than 750,000 cholecystectomies in the United States annually. Risk factors include age, gender, race, parity, obesity, and diabetes. A family history of gallstones also has been identified as a risk factor suggesting that genetics play a role in gallstone formation. However, the role of genetics in the pathogenesis of gallstone formation has not been determined. Methods: A gallbladder disease-specific questionnaire was administered to 904 healthy unrelated adult volunteers (association study). The questionnaire ascertained a history of cholecystectomy and gallstone disease in first-degree relatives, as well as medical history, demographic, and anthropometric data. A logistic regression model was used to identify risk factors for symptomatic gallstone disease in a multivariate analysis. A maximum likelihood based variance decomposition approach was then used in 1,038 individuals from 358 families (family study) to estimate the additive genetic heritability of symptomatic gallstone disease. Results: In the association study significant risk factors for symptomatic gallstone disease were female gender (relative risk 8.8, P <.003), obesity (BMI > 30, relative risk 3.7, P <.001), age > 50 (relative risk 2.5, P <.001), and a positive family history of previous cholecystectomy in a first-degree family member (relative risk 2.2, P <.01). In the family study the additive genetic heritability of symptomatic gallstones was 29% (P <.02), age and gender were significant covariates and explained 9.3% of the phenotypic variation in gallbladder disease. Conclusions: These data suggest that genetic factors are responsible for at least 30% of symptomatic gallstone disease. However, the true role of heredity in gallstone pathogenesis is probably higher because data based on symptomatic gallbladder disease underestimates the true prevalence in the population.

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