Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Jun;21(6):1428-34.
doi: 10.1097/MIB.0000000000000393.

Heritability in inflammatory bowel disease: from the first twin study to genome-wide association studies

Hannah Gordon  1 , Frederik Trier Moller, Vibeke Andersen, Marcus Harbord
Affiliations
Review

Heritability in inflammatory bowel disease: from the first twin study to genome-wide association studies

Hannah Gordon et al. Inflamm Bowel Dis. 2015 Jun.

Abstract

Since Tysk et al's pioneering analysis of the Swedish twin registry, twin and family studies continue to support a strong genetic basis of the inflammatory bowel diseases. The coefficient of heritability for siblings of inflammatory bowel disease probands is 25 to 42 for Crohn's disease and 4 to 15 for ulcerative colitis. Heritability estimates for Crohn's disease and ulcerative colitis from pooled twin studies are 0.75 and 0.67, respectively. However, this is at odds with the much lower heritability estimates from Genome-Wide Association Studies (GWAS). This "missing heritability" is likely due to shortfalls in both family studies and GWAS. The coefficient of heritability fails to account for familial shared environment. Heritability calculations from twin data are based on Falconer's method, with premises that are increasingly understood to be flawed. GWAS based heritability estimates may underestimate heritability due to incomplete linkage disequilibrium, and because some single nucleotide polypeptides (SNPs) do not reach a level of significance to allow detection. SNPs missed by GWAS include common SNPs with low penetrance and rare SNPs with high penetrance. All methods of heritability estimation regard genetic and environmental variance as separate entities, although it is now understood that there is a complex multidirectional interplay between genetic are environmental factors mediated by the microbiota, the epigenome, and the innate and acquired immune systems. Due to the limitations of heritability estimates, it is unlikely that a true value for heritability will be reached. Further work aimed at quantifying the variance explained across GWAS, epigenome-wide, and microbiota-wide association studies will help to define factors leading to inflammatory bowel disease.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Pair and proband concordance.
FIGURE 2
FIGURE 2
Falconer's equation and the assumptions underpinning this model.
FIGURE 3
FIGURE 3
The complexity of gene–exposome interactions associated with the IBD phenotype.
See this image and copyright information in PMC

References

    1. Tysk C, Lindberg E, Järnerot G, et al. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut. 1988;29:990–996. - PMC - PubMed
    1. Probert CSJ, Jayanthi V, Hughes AO, et al. Prevalence and family risk of ulcerative colitis and Crohn's disease: an epidemiological study among Europeans and South Asians in Leicestershire. Gut. 1993;34:1547–1551. - PMC - PubMed
    1. Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142:46–54.e42; quiz e30. - PubMed
    1. Kamm MA, De Cruz PP, Chan FK, et al. Inflammatory bowel disease in Asia: a systematic review. J Gastroenterol Hepatol. 2012;27:1266–1280. - PubMed
    1. Wray N, Visscher P. Estimating trait heritability. Nat Educ. 2008;1:29.

Publication types