American Gastroenterological Association Future Trends Committee Report: The Application of Genomic and Proteomic Technologies to Digestive Disease Diagnosis and Treatment and Their Likely Impact on Gastroenterology Clinical Practice

Lazaridis, Konstantinos N.; Juran, Brian D.

doi:10.1053/j.gastro.2005.06.047

Cited by 14 publications

(13 citation statements)

References 107 publications

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“…The potential of this approach to create novel hypotheses is therefore low. Overall, despite a large number of case–control studies since the late 1980s, no confirmed genetic factor for ALD had been established until recently 28 29. Failure to replicate findings from index studies was often due to inherent methodological limitations, mostly with respect to sample size and characterisation/selection of cases and controls (box 1).…”

Section: The Search For Genetic Risk Factors Of Aldmentioning

confidence: 99%

Genetic determinants of alcoholic liver disease

Stickel

Hampe

2011

Gut

123

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Alcoholic liver disease (ALD) accounts for the majority of chronic liver disease in Western countries. The spectrum of ALD includes steatosis with or without fibrosis in virtually all individuals with an alcohol consumption of >80 g/day, alcoholic steatohepatitis of variable severity in 10-35% and liver cirrhosis in approximately 15% of patients. Once cirrhosis is established, there is an annual risk for hepatocellular carcinoma of 1-2%. Environmental factors such as drinking patterns, coexisting liver disease, obesity, diet composition and comedication may modify the natural course of ALD. Twin studies have revealed a substantial contribution of genetic factors to the evolution of ALD, as demonstrated by a threefold higher disease concordance between monozygotic twins and dizygotic twins. With genotyping becoming widely available, a large number of genetic case-control studies evaluating candidate gene variants coding for proteins involved in the degradation of alcohol, mediating antioxidant defence, the evolution and counteraction of necroinflammation and formation and degradation of extracellular matrix have been published with largely unconfirmed, impeached or even disproved associations. Recently, whole genome analyses of large numbers of genetic variants in several chronic liver diseases including gallstone disease, primary sclerosing cholangitis and non-alcoholic fatty liver disease (NAFLD) have identified novel yet unconsidered candidate genes. Regarding the latter, a sequence variation within the gene coding for patatin-like phospholipase encoding 3 (PNPLA3, rs738409) was found to modulate steatosis, necroinflammation and fibrosis in NAFLD. Subsequently, the same variant was repeatedly confirmed as the first robust genetic risk factor for progressive ALD.

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Section: The Search For Genetic Risk Factors Of Aldmentioning

confidence: 99%

Genetic determinants of alcoholic liver disease

Stickel

Hampe

2011

Gut

123

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“…Complex diseases are multifactorial, the result of interplay between genes and the environment. 1,2 Thus, the strong correspondence between genotype and disease phenotype characteristics of Mendelian disorders is not present in complex disease. 3 This lack of accord makes complex diseases widely diverse in penetrance, phenotype, progression, and response to treatment.…”

Section: The Intricacy Of Complex Diseasementioning

confidence: 99%

“…In addition to twin studies, familial aggregation provides a means to estimate the level of genetic influence in complex diseases. 2 Because family members are more likely to share genetic material among themselves than with the general population, they are also more likely to share genetic characteristics associated with increased disease risk.…”

Section: The Intricacy Of Complex Diseasementioning

confidence: 99%

“…The s is calculated as the prevalence of a complex disease among siblings divided by the prevalence of the disease in the population at large. 2 Generally, the higher this number is, the greater the evidence of a genetic component to disease. However, caution should be taken when considering s values, because they may be misleading due to a substantial shared environment affect or inaccurate data on disease prevalence in the population.…”

Section: The Intricacy Of Complex Diseasementioning

confidence: 99%

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Genomics and complex liver disease: Challenges and opportunities

Juran

Lazaridis

2006

Hepatology

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The concept of genetic susceptibility in the contribution to human disease is not new. What is new is the emerging ability of the field of genomics to detect, assess, and interpret genetic variation in the study of susceptibility to development of disease. Deciphering the human genome sequence and the publication of the human haplotype map are key elements of this effort. However, we are only beginning to understand the contribution of genetic predisposition to complex liver disease through its interaction with environmental risk factors. In the coming decade, we anticipate the development of human studies to better dissect the genotype/phenotype relationship of complex liver diseases. This endeavor will require large, well-phenotyped patient populations of each disease of interest and proper study designs aimed at answering important questions of hepatic disease prognosis, pathogenesis, and treatment. Teamwork between patients, physicians, and genomics scientists can ensure that this opportunity leads to important biological discoveries and improved treatment of complex disease. (HEPATOLOGY 2006;44:1380-1390

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“…Subsequently, sizeable association studies of plausible candidate genes and genome-wide association studies will be necessary to further dissect the genetic predisposition in PSC. 16 These experimental data will provide the means for future studies of gene-gene interaction to improve the understanding of pathogenesis in PSC. Concurrently, assessment of environmental risk factors, such as smoking, should be carried out, followed by gene-environment interaction studies.…”

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confidence: 99%

American Gastroenterological Association Future Trends Committee Report: The Application of Genomic and Proteomic Technologies to Digestive Disease Diagnosis and Treatment and Their Likely Impact on Gastroenterology Clinical Practice

Cited by 14 publications

References 107 publications

Genetic determinants of alcoholic liver disease

Genetic determinants of alcoholic liver disease

Genomics and complex liver disease: Challenges and opportunities

Dissecting the genetic susceptibility for cholangiocarcinoma in primary sclerosing cholangitis

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