Brief report: Genetics of alcoholic Cirrhosis-GenomALC multinational study

the GenomALC Consortium

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: The risk of alcohol-related liver cirrhosis increases with increasing alcohol consumption, but many people with very high intake escape from liver disease. We postulate that susceptibility to alcoholic cirrhosis has a complex genetic component and propose that this can be dissected through a large and sufficiently powered genomewide association study (GWAS). Methods: The GenomALC Consortium comprises researchers from Australia, France, Germany, Switzerland, United Kingdom, and United States, with a joint aim of exploring the genetic and genomic basis of alcoholic cirrhosis. For this National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism funded study, we are recruiting high-risk drinkers who are either cases (with alcoholic cirrhosis) or controls (drinking comparable amounts over similar time, but free of significant liver disease). Extensive phenotypic data are obtained using semistructured interviews and patient records, and blood samples are collected. Results: We have successfully recruited 859 participants including 538 matched case-control samples as of September 2014, using study-specific inclusion-exclusion criteria and data collection protocols. Of these, 580 are cases (442 men and 138 women) and 279 are controls (205 men and 74 women). Duration of excessive drinking was slightly greater in cases than controls and was significantly less in women than men. Cases had significantly lower lifetime alcohol intake than controls. Both cases and controls had a high prevalence of reported parental alcohol problems, but cases were significantly more likely to report that a father with alcohol problems had died from liver disease (odds ratio 2.53, 95% confidence interval 1.31 to 4.87, p = 0.0055). Conclusions: Recruitment of participants for a GWAS of alcoholic cirrhosis has proved feasible across countries with multiple sites. Affected patients often consume less alcohol than unaffected ones, emphasizing the existence of individual vulnerability factors. Cases are more likely to report liver disease in a father with alcohol problems than controls, consistent with a potential genetic component to the risk of alcoholic cirrhosis.

Original languageEnglish
Pages (from-to)836-842
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume39
Issue number5
DOIs
StatePublished - May 1 2015

Fingerprint

Alcoholic Liver Cirrhosis
Alcohols
Liver
Liver Diseases
Fathers
Drinking
National Institute on Alcohol Abuse and Alcoholism (U.S.)
National Institutes of Health (U.S.)
Switzerland
Alcohol Drinking
Liver Cirrhosis
France
Germany
Genetics
Joints
Odds Ratio
Research Personnel
Confidence Intervals
Interviews
Blood

Keywords

  • Alcoholic liver disease
  • Cirrhosis
  • Genetic risk factors
  • Genomewide association
  • High-risk drinkers

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

Brief report : Genetics of alcoholic Cirrhosis-GenomALC multinational study. / the GenomALC Consortium.

In: Alcoholism: Clinical and Experimental Research, Vol. 39, No. 5, 01.05.2015, p. 836-842.

Research output: Contribution to journalArticle

@article{94a7e02e0d0543469cd79540124e89f5,
title = "Brief report: Genetics of alcoholic Cirrhosis-GenomALC multinational study",
abstract = "Background: The risk of alcohol-related liver cirrhosis increases with increasing alcohol consumption, but many people with very high intake escape from liver disease. We postulate that susceptibility to alcoholic cirrhosis has a complex genetic component and propose that this can be dissected through a large and sufficiently powered genomewide association study (GWAS). Methods: The GenomALC Consortium comprises researchers from Australia, France, Germany, Switzerland, United Kingdom, and United States, with a joint aim of exploring the genetic and genomic basis of alcoholic cirrhosis. For this National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism funded study, we are recruiting high-risk drinkers who are either cases (with alcoholic cirrhosis) or controls (drinking comparable amounts over similar time, but free of significant liver disease). Extensive phenotypic data are obtained using semistructured interviews and patient records, and blood samples are collected. Results: We have successfully recruited 859 participants including 538 matched case-control samples as of September 2014, using study-specific inclusion-exclusion criteria and data collection protocols. Of these, 580 are cases (442 men and 138 women) and 279 are controls (205 men and 74 women). Duration of excessive drinking was slightly greater in cases than controls and was significantly less in women than men. Cases had significantly lower lifetime alcohol intake than controls. Both cases and controls had a high prevalence of reported parental alcohol problems, but cases were significantly more likely to report that a father with alcohol problems had died from liver disease (odds ratio 2.53, 95{\%} confidence interval 1.31 to 4.87, p = 0.0055). Conclusions: Recruitment of participants for a GWAS of alcoholic cirrhosis has proved feasible across countries with multiple sites. Affected patients often consume less alcohol than unaffected ones, emphasizing the existence of individual vulnerability factors. Cases are more likely to report liver disease in a father with alcohol problems than controls, consistent with a potential genetic component to the risk of alcoholic cirrhosis.",
keywords = "Alcoholic liver disease, Cirrhosis, Genetic risk factors, Genomewide association, High-risk drinkers",
author = "{the GenomALC Consortium} and Whitfield, {John B.} and Khairunnessa Rahman and Haber, {Paul S.} and Day, {Christopher P.} and Steven Masson and Daly, {Ann K.} and Cordell, {Heather J.} and Sebastian Mueller and Seitz, {Helmut K.} and Suthat Liangpunsakul and Chi Westerhold and Tiebing Liang and Lawrence Lumeng and Tatiana Foroud and Bertrand Nalpas and Philippe Mathurin and Felix Stickel and Michael Soyka and Botwin, {Gregory J.} and Morgan, {Timothy R.} and Devanshi Seth",
year = "2015",
month = "5",
day = "1",
doi = "10.1111/acer.12693",
language = "English",
volume = "39",
pages = "836--842",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Brief report

T2 - Genetics of alcoholic Cirrhosis-GenomALC multinational study

AU - the GenomALC Consortium

AU - Whitfield, John B.

AU - Rahman, Khairunnessa

AU - Haber, Paul S.

AU - Day, Christopher P.

AU - Masson, Steven

AU - Daly, Ann K.

AU - Cordell, Heather J.

AU - Mueller, Sebastian

AU - Seitz, Helmut K.

AU - Liangpunsakul, Suthat

AU - Westerhold, Chi

AU - Liang, Tiebing

AU - Lumeng, Lawrence

AU - Foroud, Tatiana

AU - Nalpas, Bertrand

AU - Mathurin, Philippe

AU - Stickel, Felix

AU - Soyka, Michael

AU - Botwin, Gregory J.

AU - Morgan, Timothy R.

AU - Seth, Devanshi

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Background: The risk of alcohol-related liver cirrhosis increases with increasing alcohol consumption, but many people with very high intake escape from liver disease. We postulate that susceptibility to alcoholic cirrhosis has a complex genetic component and propose that this can be dissected through a large and sufficiently powered genomewide association study (GWAS). Methods: The GenomALC Consortium comprises researchers from Australia, France, Germany, Switzerland, United Kingdom, and United States, with a joint aim of exploring the genetic and genomic basis of alcoholic cirrhosis. For this National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism funded study, we are recruiting high-risk drinkers who are either cases (with alcoholic cirrhosis) or controls (drinking comparable amounts over similar time, but free of significant liver disease). Extensive phenotypic data are obtained using semistructured interviews and patient records, and blood samples are collected. Results: We have successfully recruited 859 participants including 538 matched case-control samples as of September 2014, using study-specific inclusion-exclusion criteria and data collection protocols. Of these, 580 are cases (442 men and 138 women) and 279 are controls (205 men and 74 women). Duration of excessive drinking was slightly greater in cases than controls and was significantly less in women than men. Cases had significantly lower lifetime alcohol intake than controls. Both cases and controls had a high prevalence of reported parental alcohol problems, but cases were significantly more likely to report that a father with alcohol problems had died from liver disease (odds ratio 2.53, 95% confidence interval 1.31 to 4.87, p = 0.0055). Conclusions: Recruitment of participants for a GWAS of alcoholic cirrhosis has proved feasible across countries with multiple sites. Affected patients often consume less alcohol than unaffected ones, emphasizing the existence of individual vulnerability factors. Cases are more likely to report liver disease in a father with alcohol problems than controls, consistent with a potential genetic component to the risk of alcoholic cirrhosis.

AB - Background: The risk of alcohol-related liver cirrhosis increases with increasing alcohol consumption, but many people with very high intake escape from liver disease. We postulate that susceptibility to alcoholic cirrhosis has a complex genetic component and propose that this can be dissected through a large and sufficiently powered genomewide association study (GWAS). Methods: The GenomALC Consortium comprises researchers from Australia, France, Germany, Switzerland, United Kingdom, and United States, with a joint aim of exploring the genetic and genomic basis of alcoholic cirrhosis. For this National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism funded study, we are recruiting high-risk drinkers who are either cases (with alcoholic cirrhosis) or controls (drinking comparable amounts over similar time, but free of significant liver disease). Extensive phenotypic data are obtained using semistructured interviews and patient records, and blood samples are collected. Results: We have successfully recruited 859 participants including 538 matched case-control samples as of September 2014, using study-specific inclusion-exclusion criteria and data collection protocols. Of these, 580 are cases (442 men and 138 women) and 279 are controls (205 men and 74 women). Duration of excessive drinking was slightly greater in cases than controls and was significantly less in women than men. Cases had significantly lower lifetime alcohol intake than controls. Both cases and controls had a high prevalence of reported parental alcohol problems, but cases were significantly more likely to report that a father with alcohol problems had died from liver disease (odds ratio 2.53, 95% confidence interval 1.31 to 4.87, p = 0.0055). Conclusions: Recruitment of participants for a GWAS of alcoholic cirrhosis has proved feasible across countries with multiple sites. Affected patients often consume less alcohol than unaffected ones, emphasizing the existence of individual vulnerability factors. Cases are more likely to report liver disease in a father with alcohol problems than controls, consistent with a potential genetic component to the risk of alcoholic cirrhosis.

KW - Alcoholic liver disease

KW - Cirrhosis

KW - Genetic risk factors

KW - Genomewide association

KW - High-risk drinkers

UR - http://www.scopus.com/inward/record.url?scp=84927585224&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84927585224&partnerID=8YFLogxK

U2 - 10.1111/acer.12693

DO - 10.1111/acer.12693

M3 - Article

C2 - 25872595

AN - SCOPUS:84927585224

VL - 39

SP - 836

EP - 842

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 5

ER -