Vincent Laville1, Jae H Kang2, Clara C Cousins3, Adriana I Iglesias4, Réka Nagy5, Jessica N Cooke Bailey6, Robert P Igo7, Yeunjoo E Song6, Daniel I Chasman8, William G Christen8, Peter Kraft9, Bernard A Rosner10, Frank Hu11, James F Wilson12, Puya Gharahkhani13, Alex W Hewitt14, David A Mackey15, Pirro G Hysi16, Christopher J Hammond16, Cornelia M vanDuijn17, Jonathan L Haines6, Veronique Vitart5, John H Fingert18, Michael A Hauser19, Hugues Aschard20, Janey L Wiggs3, Anthony P Khawaja21, Stuart MacGregor13, Louis R Pasquale22. 1. Department of Computational Biology, Institut Pasteur, Paris, France. 2. Channing Division of Network Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA. 3. Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA. 4. Departments of Ophthalmology and Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands. 5. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom. 6. Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. 7. Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. 8. Division of Preventive Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA. 9. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, USA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, USA. 10. Channing Division of Network Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, USA. 11. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, USA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, USA. 12. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom. 13. Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia. 14. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia; School of Medicine, Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. 15. Lions Eye Institute, Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia. 16. Department of Twin Research and Genetic Epidemiology, King's College London, United Kingdom. 17. Departments of Ophthalmology and Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands; Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. 18. Department of Ophthalmology and Visual Science, University of Iowa, Iowa City, Iowa, USA. 19. Departments of Ophthalmology and Medicine, Duke University, Durham, North Carolina, USA. 20. Department of Computational Biology, Institut Pasteur, Paris, France; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, USA. 21. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom. 22. Channing Division of Network Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: Louis.Pasquale@mssm.edu.
Abstract
PURPOSE: A genetic correlation is the proportion of phenotypic variance between traits that is shared on a genetic basis. Here we explore genetic correlations between diabetes- and glaucoma-related traits. DESIGN: Cross-sectional study. METHODS: We assembled genome-wide association study summary statistics from European-derived participants regarding diabetes-related traits like fasting blood sugar (FBS) and type 2 diabetes (T2D) and glaucoma-related traits (intraocular pressure [IOP], central corneal thickness [CCT], corneal hysteresis [CH], corneal resistance factor [CRF], cup-to-disc ratio [CDR], and primary open-angle glaucoma [POAG]). We included data from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database, the UK Biobank, and the International Glaucoma Genetics Consortium. We calculated genetic correlation (rg) between traits using linkage disequilibrium score regression. We also calculated genetic correlations between IOP, CCT, and select diabetes-related traits based on individual level phenotype data in 2 Northern European population-based samples using pedigree information and Sequential Oligogenic Linkage Analysis Routines. RESULTS: Overall, there was little rg between diabetes- and glaucoma-related traits. Specifically, we found a nonsignificant negative correlation between T2D and POAG (rg = -0.14; P = .16). Using Sequential Oligogenic Linkage Analysis Routines, the genetic correlations between measured IOP, CCT, FBS, fasting insulin, and hemoglobin A1c were null. In contrast, genetic correlations between IOP and POAG (rg ≥ 0.45; P ≤ 3.0 × 10-4) and between CDR and POAG were high (rg = 0.57; P = 2.8 × 10-10). However, genetic correlations between corneal properties (CCT, CRF, and CH) and POAG were low (rg range -0.18 to 0.11) and nonsignificant (P ≥ .07). CONCLUSION: These analyses suggest that there is limited genetic correlation between diabetes- and glaucoma-related traits.
PURPOSE: A genetic correlation is the proportion of phenotypic variance between traits that is shared on a genetic basis. Here we explore genetic correlations between diabetes- and glaucoma-related traits. DESIGN: Cross-sectional study. METHODS: We assembled genome-wide association study summary statistics from European-derived participants regarding diabetes-related traits like fasting blood sugar (FBS) and type 2 diabetes (T2D) and glaucoma-related traits (intraocular pressure [IOP], central corneal thickness [CCT], corneal hysteresis [CH], corneal resistance factor [CRF], cup-to-disc ratio [CDR], and primary open-angle glaucoma [POAG]). We included data from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database, the UK Biobank, and the International Glaucoma Genetics Consortium. We calculated genetic correlation (rg) between traits using linkage disequilibrium score regression. We also calculated genetic correlations between IOP, CCT, and select diabetes-related traits based on individual level phenotype data in 2 Northern European population-based samples using pedigree information and Sequential Oligogenic Linkage Analysis Routines. RESULTS: Overall, there was little rg between diabetes- and glaucoma-related traits. Specifically, we found a nonsignificant negative correlation between T2D and POAG (rg = -0.14; P = .16). Using Sequential Oligogenic Linkage Analysis Routines, the genetic correlations between measured IOP, CCT, FBS, fasting insulin, and hemoglobin A1c were null. In contrast, genetic correlations between IOP and POAG (rg ≥ 0.45; P ≤ 3.0 × 10-4) and between CDR and POAG were high (rg = 0.57; P = 2.8 × 10-10). However, genetic correlations between corneal properties (CCT, CRF, and CH) and POAG were low (rg range -0.18 to 0.11) and nonsignificant (P ≥ .07). CONCLUSION: These analyses suggest that there is limited genetic correlation between diabetes- and glaucoma-related traits.
Authors: Ruth McQuillan; Anne-Louise Leutenegger; Rehab Abdel-Rahman; Christopher S Franklin; Marijana Pericic; Lovorka Barac-Lauc; Nina Smolej-Narancic; Branka Janicijevic; Ozren Polasek; Albert Tenesa; Andrew K Macleod; Susan M Farrington; Pavao Rudan; Caroline Hayward; Veronique Vitart; Igor Rudan; Sarah H Wild; Malcolm G Dunlop; Alan F Wright; Harry Campbell; James F Wilson Journal: Am J Hum Genet Date: 2008-08-28 Impact factor: 11.025
Authors: Huiyuan Hou; Takuhei Shoji; Linda M Zangwill; Sasan Moghimi; Luke J Saunders; Kyle Hasenstab; Elham Ghahari; Patricia Isabel C Manalastas; Tadamichi Akagi; Mark Christopher; Rafaella C Penteado; Robert N Weinreb Journal: Am J Ophthalmol Date: 2018-02-13 Impact factor: 5.258
Authors: Richa Saxena; Marie-France Hivert; Claudia Langenberg; Toshiko Tanaka; James S Pankow; Peter Vollenweider; Valeriya Lyssenko; Nabila Bouatia-Naji; Josée Dupuis; Anne U Jackson; W H Linda Kao; Man Li; Nicole L Glazer; Alisa K Manning; Jian'an Luan; Heather M Stringham; Inga Prokopenko; Toby Johnson; Niels Grarup; Trine W Boesgaard; Cécile Lecoeur; Peter Shrader; Jeffrey O'Connell; Erik Ingelsson; David J Couper; Kenneth Rice; Kijoung Song; Camilla H Andreasen; Christian Dina; Anna Köttgen; Olivier Le Bacquer; François Pattou; Jalal Taneera; Valgerdur Steinthorsdottir; Denis Rybin; Kristin Ardlie; Michael Sampson; Lu Qi; Mandy van Hoek; Michael N Weedon; Yurii S Aulchenko; Benjamin F Voight; Harald Grallert; Beverley Balkau; Richard N Bergman; Suzette J Bielinski; Amelie Bonnefond; Lori L Bonnycastle; Knut Borch-Johnsen; Yvonne Böttcher; Eric Brunner; Thomas A Buchanan; Suzannah J Bumpstead; Christine Cavalcanti-Proença; Guillaume Charpentier; Yii-Der Ida Chen; Peter S Chines; Francis S Collins; Marilyn Cornelis; Gabriel J Crawford; Jerome Delplanque; Alex Doney; Josephine M Egan; Michael R Erdos; Mathieu Firmann; Nita G Forouhi; Caroline S Fox; Mark O Goodarzi; Jürgen Graessler; Aroon Hingorani; Bo Isomaa; Torben Jørgensen; Mika Kivimaki; Peter Kovacs; Knut Krohn; Meena Kumari; Torsten Lauritzen; Claire Lévy-Marchal; Vladimir Mayor; Jarred B McAteer; David Meyre; Braxton D Mitchell; Karen L Mohlke; Mario A Morken; Narisu Narisu; Colin N A Palmer; Ruth Pakyz; Laura Pascoe; Felicity Payne; Daniel Pearson; Wolfgang Rathmann; Annelli Sandbaek; Avan Aihie Sayer; Laura J Scott; Stephen J Sharp; Eric Sijbrands; Andrew Singleton; David S Siscovick; Nicholas L Smith; Thomas Sparsø; Amy J Swift; Holly Syddall; Gudmar Thorleifsson; Anke Tönjes; Tiinamaija Tuomi; Jaakko Tuomilehto; Timo T Valle; Gérard Waeber; Andrew Walley; Dawn M Waterworth; Eleftheria Zeggini; Jing Hua Zhao; Thomas Illig; H Erich Wichmann; James F Wilson; Cornelia van Duijn; Frank B Hu; Andrew D Morris; Timothy M Frayling; Andrew T Hattersley; Unnur Thorsteinsdottir; Kari Stefansson; Peter Nilsson; Ann-Christine Syvänen; Alan R Shuldiner; Mark Walker; Stefan R Bornstein; Peter Schwarz; Gordon H Williams; David M Nathan; Johanna Kuusisto; Markku Laakso; Cyrus Cooper; Michael Marmot; Luigi Ferrucci; Vincent Mooser; Michael Stumvoll; Ruth J F Loos; David Altshuler; Bruce M Psaty; Jerome I Rotter; Eric Boerwinkle; Torben Hansen; Oluf Pedersen; Jose C Florez; Mark I McCarthy; Michael Boehnke; Inês Barroso; Robert Sladek; Philippe Froguel; James B Meigs; Leif Groop; Nicholas J Wareham; Richard M Watanabe Journal: Nat Genet Date: 2010-01-17 Impact factor: 38.330
Authors: Michelle P Y Chan; Carlota M Grossi; Anthony P Khawaja; Jennifer L Y Yip; Kay-Tee Khaw; Praveen J Patel; Peng T Khaw; James E Morgan; Stephen A Vernon; Paul J Foster Journal: Ophthalmology Date: 2016-01-13 Impact factor: 12.079
Authors: Puya Gharahkhani; Eric Jorgenson; Pirro Hysi; Anthony P Khawaja; Sarah Pendergrass; Xikun Han; Jue Sheng Ong; Alex W Hewitt; Ayellet V Segrè; John M Rouhana; Andrew R Hamel; Robert P Igo; Helene Choquet; Ayub Qassim; Navya S Josyula; Jessica N Cooke Bailey; Pieter W M Bonnemaijer; Adriana Iglesias; Owen M Siggs; Terri L Young; Veronique Vitart; Alberta A H J Thiadens; Juha Karjalainen; Steffen Uebe; Ronald B Melles; K Saidas Nair; Robert Luben; Mark Simcoe; Nishani Amersinghe; Angela J Cree; Rene Hohn; Alicia Poplawski; Li Jia Chen; Shi-Song Rong; Tin Aung; Eranga Nishanthie Vithana; Gen Tamiya; Yukihiro Shiga; Masayuki Yamamoto; Toru Nakazawa; Hannah Currant; Ewan Birney; Xin Wang; Adam Auton; Michelle K Lupton; Nicholas G Martin; Adeyinka Ashaye; Olusola Olawoye; Susan E Williams; Stephen Akafo; Michele Ramsay; Kazuki Hashimoto; Yoichiro Kamatani; Masato Akiyama; Yukihide Momozawa; Paul J Foster; Peng T Khaw; James E Morgan; Nicholas G Strouthidis; Peter Kraft; Jae H Kang; Chi Pui Pang; Francesca Pasutto; Paul Mitchell; Andrew J Lotery; Aarno Palotie; Cornelia van Duijn; Jonathan L Haines; Chris Hammond; Louis R Pasquale; Caroline C W Klaver; Michael Hauser; Chiea Chuen Khor; David A Mackey; Michiaki Kubo; Ching-Yu Cheng; Jamie E Craig; Stuart MacGregor; Janey L Wiggs Journal: Nat Commun Date: 2021-02-24 Impact factor: 14.919
Authors: Rana Torabi; Alon Harris; Brent Siesky; Ryan Zukerman; Francesco Oddone; Sunu Mathew; Ingrida Januleviciene; Alice C Verticchio Vercellin Journal: J Ophthalmic Vis Res Date: 2021-10-25