INTRODUCTION: Serum urate is associated with BMD and may be a protective factor. However, the exact association and mechanism are still unclear. We performed a genome-wide gene-environmental interaction study (GWGEIS) to explore the interaction effects between gene and urate on BMD, using data from the UK Biobank cohort. METHODS: A total of 4575 participants for femur total BMD, 4561 participants for L1-L4 BMD, and 237799 participants for heel BMD were included in the present study. Linear regression models were used to test for associations between urate and BMD (femur total BMD, L1-L4 BMD, heel BMD) by R software. GWGEIS was conducted by PLINK 2.0 using a generalize linear model, adjusted for age, sex, weight, smoking behavior, drinking behavior, physical activity and 10 principle components for population structure. RESULTS: Results showed that urate was positively associated with femur total BMD, L1-L4 BMD and heel BMD and similar findings were observed in both the male and female subgroups. GWGEIS identified 261 genome-wide significant (P < 5.00 × 10-8) SNP × urate interaction effects for femur total BMD (rs8192585 in NOTCH4, rs116080577 in PBX1, rs9409991 in COL5A1), 17 genome-wide significant SNP × urate interaction effects for heel BMD (rs145344540 in PDE11A and rs78485379 in DKK2), 17 suggestive genome-wide SNP × urate interaction effects (P < 1.00 × 10-5) for L1-L4 BMD (rs10977015 in PTPRD). We also detected genome-wide significant and suggestive SNP × urate interaction effects for BMD in both the male and female subgroups. CONCLUSIONS: This study reported several novel candidate genes, and strengthen the evidence of the interactive effects between gene and urate on the variations of BMD.
INTRODUCTION: Serum urate is associated with BMD and may be a protective factor. However, the exact association and mechanism are still unclear. We performed a genome-wide gene-environmental interaction study (GWGEIS) to explore the interaction effects between gene and urate on BMD, using data from the UK Biobank cohort. METHODS: A total of 4575 participants for femur total BMD, 4561 participants for L1-L4 BMD, and 237799 participants for heel BMD were included in the present study. Linear regression models were used to test for associations between urate and BMD (femur total BMD, L1-L4 BMD, heel BMD) by R software. GWGEIS was conducted by PLINK 2.0 using a generalize linear model, adjusted for age, sex, weight, smoking behavior, drinking behavior, physical activity and 10 principle components for population structure. RESULTS: Results showed that urate was positively associated with femur total BMD, L1-L4 BMD and heel BMD and similar findings were observed in both the male and female subgroups. GWGEIS identified 261 genome-wide significant (P < 5.00 × 10-8) SNP × urate interaction effects for femur total BMD (rs8192585 in NOTCH4, rs116080577 in PBX1, rs9409991 in COL5A1), 17 genome-wide significant SNP × urate interaction effects for heel BMD (rs145344540 in PDE11A and rs78485379 in DKK2), 17 suggestive genome-wide SNP × urate interaction effects (P < 1.00 × 10-5) for L1-L4 BMD (rs10977015 in PTPRD). We also detected genome-wide significant and suggestive SNP × urate interaction effects for BMD in both the male and female subgroups. CONCLUSIONS: This study reported several novel candidate genes, and strengthen the evidence of the interactive effects between gene and urate on the variations of BMD.
Authors: Maria A Christou; Georgios Ntritsos; Georgios Markozannes; Fotis Koskeridis; Spyros N Nikas; David Karasik; Douglas P Kiel; Evangelos Evangelou; Evangelia E Ntzani Journal: Bone Res Date: 2020-07-01 Impact factor: 13.567
Authors: Richard Karlsson Linnér; Pietro Biroli; Edward Kong; S Fleur W Meddens; Robbee Wedow; Mark Alan Fontana; Maël Lebreton; Stephen P Tino; Abdel Abdellaoui; Anke R Hammerschlag; Michel G Nivard; Aysu Okbay; Cornelius A Rietveld; Pascal N Timshel; Maciej Trzaskowski; Ronald de Vlaming; Christian L Zünd; Yanchun Bao; Laura Buzdugan; Ann H Caplin; Chia-Yen Chen; Peter Eibich; Pierre Fontanillas; Juan R Gonzalez; Peter K Joshi; Ville Karhunen; Aaron Kleinman; Remy Z Levin; Christina M Lill; Gerardus A Meddens; Gerard Muntané; Sandra Sanchez-Roige; Frank J van Rooij; Erdogan Taskesen; Yang Wu; Futao Zhang; Adam Auton; Jason D Boardman; David W Clark; Andrew Conlin; Conor C Dolan; Urs Fischbacher; Patrick J F Groenen; Kathleen Mullan Harris; Gregor Hasler; Albert Hofman; Mohammad A Ikram; Sonia Jain; Robert Karlsson; Ronald C Kessler; Maarten Kooyman; James MacKillop; Minna Männikkö; Carlos Morcillo-Suarez; Matthew B McQueen; Klaus M Schmidt; Melissa C Smart; Matthias Sutter; A Roy Thurik; André G Uitterlinden; Jon White; Harriet de Wit; Jian Yang; Lars Bertram; Dorret I Boomsma; Tõnu Esko; Ernst Fehr; David A Hinds; Magnus Johannesson; Meena Kumari; David Laibson; Patrik K E Magnusson; Michelle N Meyer; Arcadi Navarro; Abraham A Palmer; Tune H Pers; Danielle Posthuma; Daniel Schunk; Murray B Stein; Rauli Svento; Henning Tiemeier; Paul R H J Timmers; Patrick Turley; Robert J Ursano; Gert G Wagner; James F Wilson; Jacob Gratten; James J Lee; David Cesarini; Daniel J Benjamin; Philipp D Koellinger; Jonathan P Beauchamp Journal: Nat Genet Date: 2019-01-14 Impact factor: 38.330
Authors: Hou-Feng Zheng; Vincenzo Forgetta; Yi-Hsiang Hsu; Karol Estrada; Alberto Rosello-Diez; Paul J Leo; Chitra L Dahia; Kyung Hyun Park-Min; Jonathan H Tobias; Charles Kooperberg; Aaron Kleinman; Unnur Styrkarsdottir; Ching-Ti Liu; Charlotta Uggla; Daniel S Evans; Carrie M Nielson; Klaudia Walter; Ulrika Pettersson-Kymmer; Shane McCarthy; Joel Eriksson; Tony Kwan; Mila Jhamai; Katerina Trajanoska; Yasin Memari; Josine Min; Jie Huang; Petr Danecek; Beth Wilmot; Rui Li; Wen-Chi Chou; Lauren E Mokry; Alireza Moayyeri; Melina Claussnitzer; Chia-Ho Cheng; Warren Cheung; Carolina Medina-Gómez; Bing Ge; Shu-Huang Chen; Kwangbom Choi; Ling Oei; James Fraser; Robert Kraaij; Matthew A Hibbs; Celia L Gregson; Denis Paquette; Albert Hofman; Carl Wibom; Gregory J Tranah; Mhairi Marshall; Brooke B Gardiner; Katie Cremin; Paul Auer; Li Hsu; Sue Ring; Joyce Y Tung; Gudmar Thorleifsson; Anke W Enneman; Natasja M van Schoor; Lisette C P G M de Groot; Nathalie van der Velde; Beatrice Melin; John P Kemp; Claus Christiansen; Adrian Sayers; Yanhua Zhou; Sophie Calderari; Jeroen van Rooij; Chris Carlson; Ulrike Peters; Soizik Berlivet; Josée Dostie; Andre G Uitterlinden; Stephen R Williams; Charles Farber; Daniel Grinberg; Andrea Z LaCroix; Jeff Haessler; Daniel I Chasman; Franco Giulianini; Lynda M Rose; Paul M Ridker; John A Eisman; Tuan V Nguyen; Jacqueline R Center; Xavier Nogues; Natalia Garcia-Giralt; Lenore L Launer; Vilmunder Gudnason; Dan Mellström; Liesbeth Vandenput; Najaf Amin; Cornelia M van Duijn; Magnus K Karlsson; Östen Ljunggren; Olle Svensson; Göran Hallmans; François Rousseau; Sylvie Giroux; Johanne Bussière; Pascal P Arp; Fjorda Koromani; Richard L Prince; Joshua R Lewis; Bente L Langdahl; A Pernille Hermann; Jens-Erik B Jensen; Stephen Kaptoge; Kay-Tee Khaw; Jonathan Reeve; Melissa M Formosa; Angela Xuereb-Anastasi; Kristina Åkesson; Fiona E McGuigan; Gaurav Garg; Jose M Olmos; Maria T Zarrabeitia; Jose A Riancho; Stuart H Ralston; Nerea Alonso; Xi Jiang; David Goltzman; Tomi Pastinen; Elin Grundberg; Dominique Gauguier; Eric S Orwoll; David Karasik; George Davey-Smith; Albert V Smith; Kristin Siggeirsdottir; Tamara B Harris; M Carola Zillikens; Joyce B J van Meurs; Unnur Thorsteinsdottir; Matthew T Maurano; Nicholas J Timpson; Nicole Soranzo; Richard Durbin; Scott G Wilson; Evangelia E Ntzani; Matthew A Brown; Kari Stefansson; David A Hinds; Tim Spector; L Adrienne Cupples; Claes Ohlsson; Celia M T Greenwood; Rebecca D Jackson; David W Rowe; Cynthia A Loomis; David M Evans; Cheryl L Ackert-Bicknell; Alexandra L Joyner; Emma L Duncan; Douglas P Kiel; Fernando Rivadeneira; J Brent Richards Journal: Nature Date: 2015-09-14 Impact factor: 49.962
Authors: Clare Bycroft; Colin Freeman; Desislava Petkova; Gavin Band; Lloyd T Elliott; Kevin Sharp; Allan Motyer; Damjan Vukcevic; Olivier Delaneau; Jared O'Connell; Adrian Cortes; Samantha Welsh; Alan Young; Mark Effingham; Gil McVean; Stephen Leslie; Naomi Allen; Peter Donnelly; Jonathan Marchini Journal: Nature Date: 2018-10-10 Impact factor: 49.962