BACKGROUND & AIMS: A genome-wide association study associated 5 genetic variants with hepatic steatosis (identified by computerized tomography) in individuals of European ancestry. We investigated whether these variants were associated with measures of hepatic steatosis (HS) in non-Hispanic white (NHW), non-Hispanic black, and Mexican American (MA) participants in the US population-based National Health and Nutrition Examination Survey III, phase 2. METHODS: We analyzed data from 4804 adults (1825 NHW, 1442 non-Hispanic black, and 1537 MA; 51.7% women; mean age at examination, 42.5 y); the weighted prevalence of HS was 37.3%. We investigated whether ultrasound-measured HS, with and without increased levels of alanine aminotransferase (ALT), or level of ALT alone, was associated with rs738409 (patatin-like phospholipase domain-containing protein 3 [PNPLA3]), rs2228603 (neurocan [NCAN]), rs12137855 (lysophospholipase-like 1), rs780094 (glucokinase regulatory protein [GCKR]), and rs4240624 (protein phosphatase 1, regulatory subunit 3b [PPP1R3B]) using regression modeling in an additive genetic model, controlling for age, age-squared, sex, and alcohol consumption. RESULTS: The G allele of rs738409 (PNPLA3) and the T allele of rs780094 (GCKR) were associated with HS with a high level of ALT (odds ratio [OR], 1.36; P = .01; and OR, 1.30; P = .03, respectively). The A allele of rs4240624 (PPP1R3B) and the T allele of rs2228603 (NCAN) were associated with HS (OR, 1.28; P = .03; and OR, 1.40; P = .04, respectively). Variants of PNPLA3 and NCAN were associated with ALT level among all 3 ancestries. Some single-nucleotide polymorphisms were associated with particular races or ethnicities: variants in PNPLA3, NCAN, GCKR, and PPP1R3B were associated with NHW and variants in PNPLA3 were associated with MA. No variants were associated with NHB. CONCLUSIONS: We used data from the National Health and Nutrition Examination Survey III to validate the association between rs738409 (PNPLA3), rs780094 (GCKR), and rs4240624 (PPP1R3B) with HS, with or without increased levels of ALT, among 3 different ancestries. Some, but not all, associations between variants in NCAN, lysophospholipase-like 1, GCKR, and PPP1R3B with HS (with and without increased ALT level) were significant within subpopulations.
BACKGROUND & AIMS: A genome-wide association study associated 5 genetic variants with hepatic steatosis (identified by computerized tomography) in individuals of European ancestry. We investigated whether these variants were associated with measures of hepatic steatosis (HS) in non-Hispanic white (NHW), non-Hispanic black, and Mexican American (MA) participants in the US population-based National Health and Nutrition Examination Survey III, phase 2. METHODS: We analyzed data from 4804 adults (1825 NHW, 1442 non-Hispanic black, and 1537 MA; 51.7% women; mean age at examination, 42.5 y); the weighted prevalence of HS was 37.3%. We investigated whether ultrasound-measured HS, with and without increased levels of alanine aminotransferase (ALT), or level of ALT alone, was associated with rs738409 (patatin-like phospholipase domain-containing protein 3 [PNPLA3]), rs2228603 (neurocan [NCAN]), rs12137855 (lysophospholipase-like 1), rs780094 (glucokinase regulatory protein [GCKR]), and rs4240624 (protein phosphatase 1, regulatory subunit 3b [PPP1R3B]) using regression modeling in an additive genetic model, controlling for age, age-squared, sex, and alcohol consumption. RESULTS: The G allele of rs738409 (PNPLA3) and the T allele of rs780094 (GCKR) were associated with HS with a high level of ALT (odds ratio [OR], 1.36; P = .01; and OR, 1.30; P = .03, respectively). The A allele of rs4240624 (PPP1R3B) and the T allele of rs2228603 (NCAN) were associated with HS (OR, 1.28; P = .03; and OR, 1.40; P = .04, respectively). Variants of PNPLA3 and NCAN were associated with ALT level among all 3 ancestries. Some single-nucleotide polymorphisms were associated with particular races or ethnicities: variants in PNPLA3, NCAN, GCKR, and PPP1R3B were associated with NHW and variants in PNPLA3 were associated with MA. No variants were associated with NHB. CONCLUSIONS: We used data from the National Health and Nutrition Examination Survey III to validate the association between rs738409 (PNPLA3), rs780094 (GCKR), and rs4240624 (PPP1R3B) with HS, with or without increased levels of ALT, among 3 different ancestries. Some, but not all, associations between variants in NCAN, lysophospholipase-like 1, GCKR, and PPP1R3B with HS (with and without increased ALT level) were significant within subpopulations.
Authors: Lynne E Wagenknecht; Nicholette D Palmer; Donald W Bowden; Jerome I Rotter; Jill M Norris; Julie Ziegler; Yii-Der I Chen; Steven Haffner; Ann Scherzinger; Carl D Langefeld Journal: Liver Int Date: 2011-01-13 Impact factor: 5.828
Authors: Naga Chalasani; Xiuqing Guo; Rohit Loomba; Mark O Goodarzi; Talin Haritunians; Soonil Kwon; Jinrui Cui; Kent D Taylor; Laura Wilson; Oscar W Cummings; Yii-Der Ida Chen; Jerome I Rotter Journal: Gastroenterology Date: 2010-08-11 Impact factor: 22.682
Authors: Leon A Adams; Oliver R Waters; Matthew W Knuiman; Robert R Elliott; John K Olynyk Journal: Am J Gastroenterol Date: 2009-03-17 Impact factor: 10.864
Authors: Marta I Minervini; Kristine Ruppert; Paulo Fontes; Riccardo Volpes; Giovanni Vizzini; Michael E de Vera; Salvatore Gruttadauria; Roberto Miraglia; Loredana Pipitone; J Wallis Marsh; Amadeo Marcos; Bruno Gridelli; Anthony J Demetris Journal: J Hepatol Date: 2008-12-29 Impact factor: 25.083
Authors: Cecilia M Lindgren; Iris M Heid; Joshua C Randall; Claudia Lamina; Valgerdur Steinthorsdottir; Lu Qi; Elizabeth K Speliotes; Gudmar Thorleifsson; Cristen J Willer; Blanca M Herrera; Anne U Jackson; Noha Lim; Paul Scheet; Nicole Soranzo; Najaf Amin; Yurii S Aulchenko; John C Chambers; Alexander Drong; Jian'an Luan; Helen N Lyon; Fernando Rivadeneira; Serena Sanna; Nicholas J Timpson; M Carola Zillikens; Jing Hua Zhao; Peter Almgren; Stefania Bandinelli; Amanda J Bennett; Richard N Bergman; Lori L Bonnycastle; Suzannah J Bumpstead; Stephen J Chanock; Lynn Cherkas; Peter Chines; Lachlan Coin; Cyrus Cooper; Gabriel Crawford; Angela Doering; Anna Dominiczak; Alex S F Doney; Shah Ebrahim; Paul Elliott; Michael R Erdos; Karol Estrada; Luigi Ferrucci; Guido Fischer; Nita G Forouhi; Christian Gieger; Harald Grallert; Christopher J Groves; Scott Grundy; Candace Guiducci; David Hadley; Anders Hamsten; Aki S Havulinna; Albert Hofman; Rolf Holle; John W Holloway; Thomas Illig; Bo Isomaa; Leonie C Jacobs; Karen Jameson; Pekka Jousilahti; Fredrik Karpe; Johanna Kuusisto; Jaana Laitinen; G Mark Lathrop; Debbie A Lawlor; Massimo Mangino; Wendy L McArdle; Thomas Meitinger; Mario A Morken; Andrew P Morris; Patricia Munroe; Narisu Narisu; Anna Nordström; Peter Nordström; Ben A Oostra; Colin N A Palmer; Felicity Payne; John F Peden; Inga Prokopenko; Frida Renström; Aimo Ruokonen; Veikko Salomaa; Manjinder S Sandhu; Laura J Scott; Angelo Scuteri; Kaisa Silander; Kijoung Song; Xin Yuan; Heather M Stringham; Amy J Swift; Tiinamaija Tuomi; Manuela Uda; Peter Vollenweider; Gerard Waeber; Chris Wallace; G Bragi Walters; Michael N Weedon; Jacqueline C M Witteman; Cuilin Zhang; Weihua Zhang; Mark J Caulfield; Francis S Collins; George Davey Smith; Ian N M Day; Paul W Franks; Andrew T Hattersley; Frank B Hu; Marjo-Riitta Jarvelin; Augustine Kong; Jaspal S Kooner; Markku Laakso; Edward Lakatta; Vincent Mooser; Andrew D Morris; Leena Peltonen; Nilesh J Samani; Timothy D Spector; David P Strachan; Toshiko Tanaka; Jaakko Tuomilehto; André G Uitterlinden; Cornelia M van Duijn; Nicholas J Wareham; Dawn M Waterworth; Michael Boehnke; Panos Deloukas; Leif Groop; David J Hunter; Unnur Thorsteinsdottir; David Schlessinger; H-Erich Wichmann; Timothy M Frayling; Gonçalo R Abecasis; Joel N Hirschhorn; Ruth J F Loos; Kari Stefansson; Karen L Mohlke; Inês Barroso; Mark I McCarthy Journal: PLoS Genet Date: 2009-06-26 Impact factor: 5.917
Authors: Xin Yuan; Dawn Waterworth; John R B Perry; Noha Lim; Kijoung Song; John C Chambers; Weihua Zhang; Peter Vollenweider; Heide Stirnadel; Toby Johnson; Sven Bergmann; Noam D Beckmann; Yun Li; Luigi Ferrucci; David Melzer; Dena Hernandez; Andrew Singleton; James Scott; Paul Elliott; Gerard Waeber; Lon Cardon; Timothy M Frayling; Jaspal S Kooner; Vincent Mooser Journal: Am J Hum Genet Date: 2008-10 Impact factor: 11.025
Authors: Josée Dupuis; Claudia Langenberg; Inga Prokopenko; Richa Saxena; Nicole Soranzo; Anne U Jackson; Eleanor Wheeler; Nicole L Glazer; Nabila Bouatia-Naji; Anna L Gloyn; Cecilia M Lindgren; Reedik Mägi; Andrew P Morris; Joshua Randall; Toby Johnson; Paul Elliott; Denis Rybin; Gudmar Thorleifsson; Valgerdur Steinthorsdottir; Peter Henneman; Harald Grallert; Abbas Dehghan; Jouke Jan Hottenga; Christopher S Franklin; Pau Navarro; Kijoung Song; Anuj Goel; John R B Perry; Josephine M Egan; Taina Lajunen; Niels Grarup; Thomas Sparsø; Alex Doney; Benjamin F Voight; Heather M Stringham; Man Li; Stavroula Kanoni; Peter Shrader; Christine Cavalcanti-Proença; Meena Kumari; Lu Qi; Nicholas J Timpson; Christian Gieger; Carina Zabena; Ghislain Rocheleau; Erik Ingelsson; Ping An; Jeffrey O'Connell; Jian'an Luan; Amanda Elliott; Steven A McCarroll; Felicity Payne; Rosa Maria Roccasecca; François Pattou; Praveen Sethupathy; Kristin Ardlie; Yavuz Ariyurek; Beverley Balkau; Philip Barter; John P Beilby; Yoav Ben-Shlomo; Rafn Benediktsson; Amanda J Bennett; Sven Bergmann; Murielle Bochud; Eric Boerwinkle; Amélie Bonnefond; Lori L Bonnycastle; Knut Borch-Johnsen; Yvonne Böttcher; Eric Brunner; Suzannah J Bumpstead; Guillaume Charpentier; Yii-Der Ida Chen; Peter Chines; Robert Clarke; Lachlan J M Coin; Matthew N Cooper; Marilyn Cornelis; Gabe Crawford; Laura Crisponi; Ian N M Day; Eco J C de Geus; Jerome Delplanque; Christian Dina; Michael R Erdos; Annette C Fedson; Antje Fischer-Rosinsky; Nita G Forouhi; Caroline S Fox; Rune Frants; Maria Grazia Franzosi; Pilar Galan; Mark O Goodarzi; Jürgen Graessler; Christopher J Groves; Scott Grundy; Rhian Gwilliam; Ulf Gyllensten; Samy Hadjadj; Göran Hallmans; Naomi Hammond; Xijing Han; Anna-Liisa Hartikainen; Neelam Hassanali; Caroline Hayward; Simon C Heath; Serge Hercberg; Christian Herder; Andrew A Hicks; David R Hillman; Aroon D Hingorani; Albert Hofman; Jennie Hui; Joe Hung; Bo Isomaa; Paul R V Johnson; Torben Jørgensen; Antti Jula; Marika Kaakinen; Jaakko Kaprio; Y Antero Kesaniemi; Mika Kivimaki; Beatrice Knight; Seppo Koskinen; Peter Kovacs; Kirsten Ohm Kyvik; G Mark Lathrop; Debbie A Lawlor; Olivier Le Bacquer; Cécile Lecoeur; Yun Li; Valeriya Lyssenko; Robert Mahley; Massimo Mangino; Alisa K Manning; María Teresa Martínez-Larrad; Jarred B McAteer; Laura J McCulloch; Ruth McPherson; Christa Meisinger; David Melzer; David Meyre; Braxton D Mitchell; Mario A Morken; Sutapa Mukherjee; Silvia Naitza; Narisu Narisu; Matthew J Neville; Ben A Oostra; Marco Orrù; Ruth Pakyz; Colin N A Palmer; Giuseppe Paolisso; Cristian Pattaro; Daniel Pearson; John F Peden; Nancy L Pedersen; Markus Perola; Andreas F H Pfeiffer; Irene Pichler; Ozren Polasek; Danielle Posthuma; Simon C Potter; Anneli Pouta; Michael A Province; Bruce M Psaty; Wolfgang Rathmann; Nigel W Rayner; Kenneth Rice; Samuli Ripatti; Fernando Rivadeneira; Michael Roden; Olov Rolandsson; Annelli Sandbaek; Manjinder Sandhu; Serena Sanna; Avan Aihie Sayer; Paul Scheet; Laura J Scott; Udo Seedorf; Stephen J Sharp; Beverley Shields; Gunnar Sigurethsson; Eric J G Sijbrands; Angela Silveira; Laila Simpson; Andrew Singleton; Nicholas L Smith; Ulla Sovio; Amy Swift; Holly Syddall; Ann-Christine Syvänen; Toshiko Tanaka; Barbara Thorand; Jean Tichet; Anke Tönjes; Tiinamaija Tuomi; André G Uitterlinden; Ko Willems van Dijk; Mandy van Hoek; Dhiraj Varma; Sophie Visvikis-Siest; Veronique Vitart; Nicole Vogelzangs; Gérard Waeber; Peter J Wagner; Andrew Walley; G Bragi Walters; Kim L Ward; Hugh Watkins; Michael N Weedon; Sarah H Wild; Gonneke Willemsen; Jaqueline C M Witteman; John W G Yarnell; Eleftheria Zeggini; Diana Zelenika; Björn Zethelius; Guangju Zhai; Jing Hua Zhao; M Carola Zillikens; Ingrid B Borecki; Ruth J F Loos; Pierre Meneton; Patrik K E Magnusson; David M Nathan; Gordon H Williams; Andrew T Hattersley; Kaisa Silander; Veikko Salomaa; George Davey Smith; Stefan R Bornstein; Peter Schwarz; Joachim Spranger; Fredrik Karpe; Alan R Shuldiner; Cyrus Cooper; George V Dedoussis; Manuel Serrano-Ríos; Andrew D Morris; Lars Lind; Lyle J Palmer; Frank B Hu; Paul W Franks; Shah Ebrahim; Michael Marmot; W H Linda Kao; James S Pankow; Michael J Sampson; Johanna Kuusisto; Markku Laakso; Torben Hansen; Oluf Pedersen; Peter Paul Pramstaller; H Erich Wichmann; Thomas Illig; Igor Rudan; Alan F Wright; Michael Stumvoll; Harry Campbell; James F Wilson; Richard N Bergman; Thomas A Buchanan; Francis S Collins; Karen L Mohlke; Jaakko Tuomilehto; Timo T Valle; David Altshuler; Jerome I Rotter; David S Siscovick; Brenda W J H Penninx; Dorret I Boomsma; Panos Deloukas; Timothy D Spector; Timothy M Frayling; Luigi Ferrucci; Augustine Kong; Unnur Thorsteinsdottir; Kari Stefansson; Cornelia M van Duijn; Yurii S Aulchenko; Antonio Cao; Angelo Scuteri; David Schlessinger; Manuela Uda; Aimo Ruokonen; Marjo-Riitta Jarvelin; Dawn M Waterworth; Peter Vollenweider; Leena Peltonen; Vincent Mooser; Goncalo R Abecasis; Nicholas J Wareham; Robert Sladek; Philippe Froguel; Richard M Watanabe; James B Meigs; Leif Groop; Michael Boehnke; Mark I McCarthy; Jose C Florez; Inês Barroso Journal: Nat Genet Date: 2010-01-17 Impact factor: 38.330
Authors: Stefano Romeo; Julia Kozlitina; Chao Xing; Alexander Pertsemlidis; David Cox; Len A Pennacchio; Eric Boerwinkle; Jonathan C Cohen; Helen H Hobbs Journal: Nat Genet Date: 2008-09-25 Impact factor: 38.330
Authors: Cristen J Willer; Elizabeth K Speliotes; Ruth J F Loos; Shengxu Li; Cecilia M Lindgren; Iris M Heid; Sonja I Berndt; Amanda L Elliott; Anne U Jackson; Claudia Lamina; Guillaume Lettre; Noha Lim; Helen N Lyon; Steven A McCarroll; Konstantinos Papadakis; Lu Qi; Joshua C Randall; Rosa Maria Roccasecca; Serena Sanna; Paul Scheet; Michael N Weedon; Eleanor Wheeler; Jing Hua Zhao; Leonie C Jacobs; Inga Prokopenko; Nicole Soranzo; Toshiko Tanaka; Nicholas J Timpson; Peter Almgren; Amanda Bennett; Richard N Bergman; Sheila A Bingham; Lori L Bonnycastle; Morris Brown; Noël P Burtt; Peter Chines; Lachlan Coin; Francis S Collins; John M Connell; Cyrus Cooper; George Davey Smith; Elaine M Dennison; Parimal Deodhar; Paul Elliott; Michael R Erdos; Karol Estrada; David M Evans; Lauren Gianniny; Christian Gieger; Christopher J Gillson; Candace Guiducci; Rachel Hackett; David Hadley; Alistair S Hall; Aki S Havulinna; Johannes Hebebrand; Albert Hofman; Bo Isomaa; Kevin B Jacobs; Toby Johnson; Pekka Jousilahti; Zorica Jovanovic; Kay-Tee Khaw; Peter Kraft; Mikko Kuokkanen; Johanna Kuusisto; Jaana Laitinen; Edward G Lakatta; Jian'an Luan; Robert N Luben; Massimo Mangino; Wendy L McArdle; Thomas Meitinger; Antonella Mulas; Patricia B Munroe; Narisu Narisu; Andrew R Ness; Kate Northstone; Stephen O'Rahilly; Carolin Purmann; Matthew G Rees; Martin Ridderstråle; Susan M Ring; Fernando Rivadeneira; Aimo Ruokonen; Manjinder S Sandhu; Jouko Saramies; Laura J Scott; Angelo Scuteri; Kaisa Silander; Matthew A Sims; Kijoung Song; Jonathan Stephens; Suzanne Stevens; Heather M Stringham; Y C Loraine Tung; Timo T Valle; Cornelia M Van Duijn; Karani S Vimaleswaran; Peter Vollenweider; Gerard Waeber; Chris Wallace; Richard M Watanabe; Dawn M Waterworth; Nicholas Watkins; Jacqueline C M Witteman; Eleftheria Zeggini; Guangju Zhai; M Carola Zillikens; David Altshuler; Mark J Caulfield; Stephen J Chanock; I Sadaf Farooqi; Luigi Ferrucci; Jack M Guralnik; Andrew T Hattersley; Frank B Hu; Marjo-Riitta Jarvelin; Markku Laakso; Vincent Mooser; Ken K Ong; Willem H Ouwehand; Veikko Salomaa; Nilesh J Samani; Timothy D Spector; Tiinamaija Tuomi; Jaakko Tuomilehto; Manuela Uda; André G Uitterlinden; Nicholas J Wareham; Panagiotis Deloukas; Timothy M Frayling; Leif C Groop; Richard B Hayes; David J Hunter; Karen L Mohlke; Leena Peltonen; David Schlessinger; David P Strachan; H-Erich Wichmann; Mark I McCarthy; Michael Boehnke; Inês Barroso; Gonçalo R Abecasis; Joel N Hirschhorn Journal: Nat Genet Date: 2008-12-14 Impact factor: 38.330
Authors: J E Nelson; P Handa; B Aouizerat; L Wilson; L A Vemulakonda; M M Yeh; K V Kowdley Journal: Aliment Pharmacol Ther Date: 2016-10-11 Impact factor: 8.171
Authors: Y Liu; C A Fernandez; C Smith; W Yang; C Cheng; J C Panetta; N Kornegay; C Liu; L B Ramsey; S E Karol; L J Janke; E C Larsen; N Winick; W L Carroll; M L Loh; E A Raetz; S P Hunger; M Devidas; J J Yang; C G Mullighan; J Zhang; W E Evans; S Jeha; C-H Pui; M V Relling Journal: Clin Pharmacol Ther Date: 2017-04-04 Impact factor: 6.875
Authors: Yvonne N Flores; Rafael Velázquez-Cruz; Paula Ramírez; Manuel Bañuelos; Zuo-Feng Zhang; Hal F Yee; Shen-Chih Chang; Samuel Canizales-Quinteros; Manuel Quiterio; Guillermo Cabrera-Alvarez; Nelly Patiño; Jorge Salmerón Journal: Mol Biol Rep Date: 2016-10-17 Impact factor: 2.316