A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis

Stephan Buch; Felix Stickel; Eric Trépo; Michael Way; Alexander Herrmann; Hans Dieter Nischalke; Mario Brosch; Jonas Rosendahl; Thomas Berg; Monika Ridinger; Marcella Rietschel; Andrew McQuillin; Josef Frank; Falk Kiefer; Stefan Schreiber; Wolfgang Lieb; Michael Soyka; Nasser Semmo; Elmar Aigner; Christian Datz; Renate Schmelz; Stefan Brückner; Sebastian Zeissig; Anna Magdalena Stephan; Norbert Wodarz; Jacques Devière; Nicolas Clumeck; Christoph Sarrazin; Frank Lammert; Thierry Gustot; Pierre Deltenre; Henry Völzke; Markus M. Lerch; Julia Mayerle; Florian Eyer; Clemens Schafmayer; Sven Cichon; Markus M. Nöthen; Michael Nothnagel; David Ellinghaus; Klaus Huse; Andre Franke; Steffen Zopf; Claus Hellerbrand; Christophe Moreno; Denis Franchimont; Marsha Y. Morgan; Jochen Hampe

doi:10.1038/ng.3417

A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis

Stephan Buch, Felix Stickel, Eric Trépo, Michael Way, Alexander Herrmann, Hans Dieter Nischalke, Mario Brosch, Jonas Rosendahl, Thomas Berg, Monika Ridinger, Marcella Rietschel, Andrew McQuillin, Josef Frank, Falk Kiefer, Stefan Schreiber, Wolfgang Lieb, Michael Soyka, Nasser Semmo, Elmar Aigner, Christian DatzRenate Schmelz, Stefan Brückner, Sebastian Zeissig, Anna Magdalena Stephan, Norbert Wodarz, Jacques Devière, Nicolas Clumeck, Christoph Sarrazin, Frank Lammert, Thierry Gustot, Pierre Deltenre, Henry Völzke, Markus M. Lerch, Julia Mayerle, Florian Eyer, Clemens Schafmayer, Sven Cichon, Markus M. Nöthen, Michael Nothnagel, David Ellinghaus, Klaus Huse, Andre Franke, Steffen Zopf, Claus Hellerbrand, Christophe Moreno, Denis Franchimont, Marsha Y. Morgan, Jochen Hampe

Medicine and Health

Research output: Contribution to journal › Article › peer-review

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Abstract

Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world. We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independent European cohorts (1,148 cases and 922 controls). We identified variants in the MBOAT7 (P = 1.03 × 10^-9) and TM6SF2 (P = 7.89 × 10^-10) genes as new risk loci and confirmed rs738409 in PNPLA3 as an important risk locus for alcohol-related cirrhosis (P = 1.54 × 10^-48) at a genome-wide level of significance. These three loci have a role in lipid processing, suggesting that lipid turnover is important in the pathogenesis of alcohol-related cirrhosis.

Original language	English
Pages (from-to)	1443-1448
Number of pages	6
Journal	Nature Genetics
Volume	47
Issue number	12
DOIs	https://doi.org/10.1038/ng.3417
State	Published - 1 Dec 2015

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Buch, S., Stickel, F., Trépo, E., Way, M., Herrmann, A., Nischalke, H. D., Brosch, M., Rosendahl, J., Berg, T., Ridinger, M., Rietschel, M., McQuillin, A., Frank, J., Kiefer, F., Schreiber, S., Lieb, W., Soyka, M., Semmo, N., Aigner, E., ... Hampe, J. (2015). A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis. Nature Genetics, 47(12), 1443-1448. https://doi.org/10.1038/ng.3417

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title = "A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis",

abstract = "Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world. We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independent European cohorts (1,148 cases and 922 controls). We identified variants in the MBOAT7 (P = 1.03 × 10-9) and TM6SF2 (P = 7.89 × 10-10) genes as new risk loci and confirmed rs738409 in PNPLA3 as an important risk locus for alcohol-related cirrhosis (P = 1.54 × 10-48) at a genome-wide level of significance. These three loci have a role in lipid processing, suggesting that lipid turnover is important in the pathogenesis of alcohol-related cirrhosis.",

author = "Stephan Buch and Felix Stickel and Eric Tr{\'e}po and Michael Way and Alexander Herrmann and Nischalke, {Hans Dieter} and Mario Brosch and Jonas Rosendahl and Thomas Berg and Monika Ridinger and Marcella Rietschel and Andrew McQuillin and Josef Frank and Falk Kiefer and Stefan Schreiber and Wolfgang Lieb and Michael Soyka and Nasser Semmo and Elmar Aigner and Christian Datz and Renate Schmelz and Stefan Br{\"u}ckner and Sebastian Zeissig and Stephan, {Anna Magdalena} and Norbert Wodarz and Jacques Devi{\`e}re and Nicolas Clumeck and Christoph Sarrazin and Frank Lammert and Thierry Gustot and Pierre Deltenre and Henry V{\"o}lzke and Lerch, {Markus M.} and Julia Mayerle and Florian Eyer and Clemens Schafmayer and Sven Cichon and N{\"o}then, {Markus M.} and Michael Nothnagel and David Ellinghaus and Klaus Huse and Andre Franke and Steffen Zopf and Claus Hellerbrand and Christophe Moreno and Denis Franchimont and Morgan, {Marsha Y.} and Jochen Hampe",

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Buch, S, Stickel, F, Trépo, E, Way, M, Herrmann, A, Nischalke, HD, Brosch, M, Rosendahl, J, Berg, T, Ridinger, M, Rietschel, M, McQuillin, A, Frank, J, Kiefer, F, Schreiber, S, Lieb, W, Soyka, M, Semmo, N, Aigner, E, Datz, C, Schmelz, R, Brückner, S, Zeissig, S, Stephan, AM, Wodarz, N, Devière, J, Clumeck, N, Sarrazin, C, Lammert, F, Gustot, T, Deltenre, P, Völzke, H, Lerch, MM, Mayerle, J, Eyer, F, Schafmayer, C, Cichon, S, Nöthen, MM, Nothnagel, M, Ellinghaus, D, Huse, K, Franke, A, Zopf, S, Hellerbrand, C, Moreno, C, Franchimont, D, Morgan, MY & Hampe, J 2015, 'A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis', Nature Genetics, vol. 47, no. 12, pp. 1443-1448. https://doi.org/10.1038/ng.3417

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AU - Buch, Stephan

AU - Stickel, Felix

AU - Trépo, Eric

AU - Way, Michael

AU - Herrmann, Alexander

AU - Nischalke, Hans Dieter

AU - Brosch, Mario

AU - Rosendahl, Jonas

AU - Berg, Thomas

AU - Ridinger, Monika

AU - Rietschel, Marcella

AU - McQuillin, Andrew

AU - Frank, Josef

AU - Kiefer, Falk

AU - Schreiber, Stefan

AU - Lieb, Wolfgang

AU - Soyka, Michael

AU - Semmo, Nasser

AU - Aigner, Elmar

AU - Datz, Christian

AU - Schmelz, Renate

AU - Brückner, Stefan

AU - Zeissig, Sebastian

AU - Stephan, Anna Magdalena

AU - Wodarz, Norbert

AU - Devière, Jacques

AU - Clumeck, Nicolas

AU - Sarrazin, Christoph

AU - Lammert, Frank

AU - Gustot, Thierry

AU - Deltenre, Pierre

AU - Völzke, Henry

AU - Lerch, Markus M.

AU - Mayerle, Julia

AU - Eyer, Florian

AU - Schafmayer, Clemens

AU - Cichon, Sven

AU - Nöthen, Markus M.

AU - Nothnagel, Michael

AU - Ellinghaus, David

AU - Huse, Klaus

AU - Franke, Andre

AU - Zopf, Steffen

AU - Hellerbrand, Claus

AU - Moreno, Christophe

AU - Franchimont, Denis

AU - Morgan, Marsha Y.

AU - Hampe, Jochen

PY - 2015/12/1

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AB - Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world. We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independent European cohorts (1,148 cases and 922 controls). We identified variants in the MBOAT7 (P = 1.03 × 10-9) and TM6SF2 (P = 7.89 × 10-10) genes as new risk loci and confirmed rs738409 in PNPLA3 as an important risk locus for alcohol-related cirrhosis (P = 1.54 × 10-48) at a genome-wide level of significance. These three loci have a role in lipid processing, suggesting that lipid turnover is important in the pathogenesis of alcohol-related cirrhosis.

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JO - Nature Genetics

JF - Nature Genetics

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ER -

A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis

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