Victoria L Buchanan1, Yujie Wang1, Estela Blanco2, Mariaelisa Graff1, Cecilia Albala3, Raquel Burrows3, José L Santos4, Bárbara Angel3, Betsy Lozoff5, Venkata Saroja Voruganti6, Xiuqing Guo7, Kent D Taylor7, Yii-Der Ida Chen7, Jie Yao7, Jingyi Tan7, Carolina Downie1, Heather M Highland1, Anne E Justice1,8, Sheila Gahagan2, Kari E North1. 1. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 2. Division of Academic General Pediatrics, Child Development and Community Health, University of California at San Diego, San Diego, California, USA. 3. Department of Public Health Nutrition, Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile. 4. Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. 5. Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA. 6. Department of Nutrition and UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA. 7. The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA. 8. Department of Population Health Sciences, Geisinger, Danville, Pennsylvania, USA.
Abstract
BACKGROUND: The genetic underpinnings of glycemic traits have been understudied in adolescent and Hispanic/Latino (H/L) populations in comparison to adults and populations of European ancestry. OBJECTIVE: To identify genetic factors underlying glycemic traits in an adolescent H/L population. METHODS: We conducted a genome-wide association study (GWAS) of fasting glucose (FG) and fasting insulin (FI) in H/L adolescents from the Santiago Longitudinal Study. RESULTS: We identified one novel variant positioned in the CSMD1 gene on chromosome 8 (rs77465890, effect allele frequency = 0.10) that was associated with FI (β = -0.299, SE = 0.054, p = 2.72×10-8 ) and was only slightly attenuated after adjusting for body mass index z-scores (β = -0.252, SE = 0.047, p = 1.03×10-7 ). We demonstrated directionally consistent, but not statistically significant results in African and Hispanic adults of the Population Architecture Using Genomics and Epidemiology Consortium. We also identified secondary signals for two FG loci after conditioning on known variants, which demonstrate allelic heterogeneity in well-known glucose loci. CONCLUSION: Our results exemplify the importance of including populations with diverse ancestral origin and adolescent participants in GWAS of glycemic traits to uncover novel risk loci and expand our understanding of disease aetiology.
BACKGROUND: The genetic underpinnings of glycemic traits have been understudied in adolescent and Hispanic/Latino (H/L) populations in comparison to adults and populations of European ancestry. OBJECTIVE: To identify genetic factors underlying glycemic traits in an adolescent H/L population. METHODS: We conducted a genome-wide association study (GWAS) of fasting glucose (FG) and fasting insulin (FI) in H/L adolescents from the Santiago Longitudinal Study. RESULTS: We identified one novel variant positioned in the CSMD1 gene on chromosome 8 (rs77465890, effect allele frequency = 0.10) that was associated with FI (β = -0.299, SE = 0.054, p = 2.72×10-8 ) and was only slightly attenuated after adjusting for body mass index z-scores (β = -0.252, SE = 0.047, p = 1.03×10-7 ). We demonstrated directionally consistent, but not statistically significant results in African and Hispanic adults of the Population Architecture Using Genomics and Epidemiology Consortium. We also identified secondary signals for two FG loci after conditioning on known variants, which demonstrate allelic heterogeneity in well-known glucose loci. CONCLUSION: Our results exemplify the importance of including populations with diverse ancestral origin and adolescent participants in GWAS of glycemic traits to uncover novel risk loci and expand our understanding of disease aetiology.
Authors: K Ogurtsova; J D da Rocha Fernandes; Y Huang; U Linnenkamp; L Guariguata; N H Cho; D Cavan; J E Shaw; L E Makaroff Journal: Diabetes Res Clin Pract Date: 2017-03-31 Impact factor: 5.602
Authors: John C Rausch; Joel E Lavine; Naga Chalasani; Xiuqing Guo; Soonil Kwon; Jeffrey B Schwimmer; Jean P Molleston; Rohit Loomba; Elizabeth M Brunt; Yii-Der Ida Chen; Mark O Goodarzi; Kent D Taylor; Katherine P Yates; Jerome I Rotter Journal: J Pediatr Gastroenterol Nutr Date: 2018-05 Impact factor: 2.839
Authors: Alexessander Couto Alves; N Maneka G De Silva; Ville Karhunen; Ulla Sovio; Shikta Das; H Rob Taal; Nicole M Warrington; Alexandra M Lewin; Marika Kaakinen; Diana L Cousminer; Elisabeth Thiering; Nicholas J Timpson; Tom A Bond; Estelle Lowry; Christopher D Brown; Xavier Estivill; Virpi Lindi; Jonathan P Bradfield; Frank Geller; Doug Speed; Lachlan J M Coin; Marie Loh; Sheila J Barton; Lawrence J Beilin; Hans Bisgaard; Klaus Bønnelykke; Rohia Alili; Ida J Hatoum; Katharina Schramm; Rufus Cartwright; Marie-Aline Charles; Vincenzo Salerno; Karine Clément; Annique A J Claringbould; Cornelia M van Duijn; Elena Moltchanova; Johan G Eriksson; Cathy Elks; Bjarke Feenstra; Claudia Flexeder; Stephen Franks; Timothy M Frayling; Rachel M Freathy; Paul Elliott; Elisabeth Widén; Hakon Hakonarson; Andrew T Hattersley; Alina Rodriguez; Marco Banterle; Joachim Heinrich; Barbara Heude; John W Holloway; Albert Hofman; Elina Hyppönen; Hazel Inskip; Lee M Kaplan; Asa K Hedman; Esa Läärä; Holger Prokisch; Harald Grallert; Timo A Lakka; Debbie A Lawlor; Mads Melbye; Tarunveer S Ahluwalia; Marcella Marinelli; Iona Y Millwood; Lyle J Palmer; Craig E Pennell; John R Perry; Susan M Ring; Markku J Savolainen; Fernando Rivadeneira; Marie Standl; Jordi Sunyer; Carla M T Tiesler; Andre G Uitterlinden; William Schierding; Justin M O'Sullivan; Inga Prokopenko; Karl-Heinz Herzig; George Davey Smith; Paul O'Reilly; Janine F Felix; Jessica L Buxton; Alexandra I F Blakemore; Ken K Ong; Vincent W V Jaddoe; Struan F A Grant; Sylvain Sebert; Mark I McCarthy; Marjo-Riitta Järvelin Journal: Sci Adv Date: 2019-09-04 Impact factor: 14.136
Authors: Alisa K Manning; Marie-France Hivert; Robert A Scott; Jonna L Grimsby; Nabila Bouatia-Naji; Han Chen; Denis Rybin; Ching-Ti Liu; Lawrence F Bielak; Inga Prokopenko; Najaf Amin; Daniel Barnes; Gemma Cadby; Jouke-Jan Hottenga; Erik Ingelsson; Anne U Jackson; Toby Johnson; Stavroula Kanoni; Claes Ladenvall; Vasiliki Lagou; Jari Lahti; Cecile Lecoeur; Yongmei Liu; Maria Teresa Martinez-Larrad; May E Montasser; Pau Navarro; John R B Perry; Laura J Rasmussen-Torvik; Perttu Salo; Naveed Sattar; Dmitry Shungin; Rona J Strawbridge; Toshiko Tanaka; Cornelia M van Duijn; Ping An; Mariza de Andrade; Jeanette S Andrews; Thor Aspelund; Mustafa Atalay; Yurii Aulchenko; Beverley Balkau; Stefania Bandinelli; Jacques S Beckmann; John P Beilby; Claire Bellis; Richard N Bergman; John Blangero; Mladen Boban; Michael Boehnke; Eric Boerwinkle; Lori L Bonnycastle; Dorret I Boomsma; Ingrid B Borecki; Yvonne Böttcher; Claude Bouchard; Eric Brunner; Danijela Budimir; Harry Campbell; Olga Carlson; Peter S Chines; Robert Clarke; Francis S Collins; Arturo Corbatón-Anchuelo; David Couper; Ulf de Faire; George V Dedoussis; Panos Deloukas; Maria Dimitriou; Josephine M Egan; Gudny Eiriksdottir; Michael R Erdos; Johan G Eriksson; Elodie Eury; Luigi Ferrucci; Ian Ford; Nita G Forouhi; Caroline S Fox; Maria Grazia Franzosi; Paul W Franks; Timothy M Frayling; Philippe Froguel; Pilar Galan; Eco de Geus; Bruna Gigante; Nicole L Glazer; Anuj Goel; Leif Groop; Vilmundur Gudnason; Göran Hallmans; Anders Hamsten; Ola Hansson; Tamara B Harris; Caroline Hayward; Simon Heath; Serge Hercberg; Andrew A Hicks; Aroon Hingorani; Albert Hofman; Jennie Hui; Joseph Hung; Marjo-Riitta Jarvelin; Min A Jhun; Paul C D Johnson; J Wouter Jukema; Antti Jula; W H Kao; Jaakko Kaprio; Sharon L R Kardia; Sirkka Keinanen-Kiukaanniemi; Mika Kivimaki; Ivana Kolcic; Peter Kovacs; Meena Kumari; Johanna Kuusisto; Kirsten Ohm Kyvik; Markku Laakso; Timo Lakka; Lars Lannfelt; G Mark Lathrop; Lenore J Launer; Karin Leander; Guo Li; Lars Lind; Jaana Lindstrom; Stéphane Lobbens; Ruth J F Loos; Jian'an Luan; Valeriya Lyssenko; Reedik Mägi; Patrik K E Magnusson; Michael Marmot; Pierre Meneton; Karen L Mohlke; Vincent Mooser; Mario A Morken; Iva Miljkovic; Narisu Narisu; Jeff O'Connell; Ken K Ong; Ben A Oostra; Lyle J Palmer; Aarno Palotie; James S Pankow; John F Peden; Nancy L Pedersen; Marina Pehlic; Leena Peltonen; Brenda Penninx; Marijana Pericic; Markus Perola; Louis Perusse; Patricia A Peyser; Ozren Polasek; Peter P Pramstaller; Michael A Province; Katri Räikkönen; Rainer Rauramaa; Emil Rehnberg; Ken Rice; Jerome I Rotter; Igor Rudan; Aimo Ruokonen; Timo Saaristo; Maria Sabater-Lleal; Veikko Salomaa; David B Savage; Richa Saxena; Peter Schwarz; Udo Seedorf; Bengt Sennblad; Manuel Serrano-Rios; Alan R Shuldiner; Eric J G Sijbrands; David S Siscovick; Johannes H Smit; Kerrin S Small; Nicholas L Smith; Albert Vernon Smith; Alena Stančáková; Kathleen Stirrups; Michael Stumvoll; Yan V Sun; Amy J Swift; Anke Tönjes; Jaakko Tuomilehto; Stella Trompet; Andre G Uitterlinden; Matti Uusitupa; Max Vikström; Veronique Vitart; Marie-Claude Vohl; Benjamin F Voight; Peter Vollenweider; Gerard Waeber; Dawn M Waterworth; Hugh Watkins; Eleanor Wheeler; Elisabeth Widen; Sarah H Wild; Sara M Willems; Gonneke Willemsen; James F Wilson; Jacqueline C M Witteman; Alan F Wright; Hanieh Yaghootkar; Diana Zelenika; Tatijana Zemunik; Lina Zgaga; Nicholas J Wareham; Mark I McCarthy; Ines Barroso; Richard M Watanabe; Jose C Florez; Josée Dupuis; James B Meigs; Claudia Langenberg Journal: Nat Genet Date: 2012-05-13 Impact factor: 38.330