AIMS/HYPOTHESIS: Multiple genetic variants are associated with type 2 diabetes-related traits in Europeans, but their role in South Asian populations needs further study. We hypothesised that genetic variants associated with diabetes-related traits in Europeans would explain a similar proportion of phenotypic variance in a Pakistani population and could be used in Mendelian randomisation analyses. METHODS: We used data from 2,131 individuals from the Control of Blood Pressure and Risk Attenuation Trial (COBRA) in Karachi, Pakistan. Individuals were aged 40 years or older. RESULTS: Combining information from multiple genetic variants showed that fasting glucose, BMI, triacylglycerol, and systolic and diastolic blood pressure variants explained 2.9%, 0.7%, 5.5%, 1.2% and 1.8% of the variance in those traits respectively. Genetic risk scores of fasting glucose, triacylglycerol, BMI, systolic blood pressure and diastolic blood pressure variants were associated with these traits, with per allele SD effects of 0.057 (95% CI 0.041, 0.074), p=3.44 × 10(-12), 0.130 (95% CI 0.105, 0.155), p=2.9 × 10(-21), 0.04 (95% CI 0.014, 0.072), p=0.004, 0.031 (95% CI 0.016, 0.047), p=7.9 × 10(-5), 0.028 (95% CI 0.015, 0.042), p = 5.5 × 10(-5), respectively. These effects are consistent with those observed in Europeans, except that the effect of triacylglycerol variants in South Asians was slightly lower. Mendelian randomisation provided evidence that genetically influenced, raised triacylglycerol levels do not causally affect type 2 diabetes risk to the extent predicted from observational data (p=0.0003 for difference between observed and instrumental variables correlations). CONCLUSIONS/ INTERPRETATION: Genetic variants identified in Europeans are associated with type 2 diabetes-related traits in Pakistanis, with comparable effect sizes. Larger studies are needed to perform adequately powered Mendelian randomisation and help dissect the relationships between type 2 diabetes-related traits in diverse South Asian subgroups.
AIMS/HYPOTHESIS: Multiple genetic variants are associated with type 2 diabetes-related traits in Europeans, but their role in South Asian populations needs further study. We hypothesised that genetic variants associated with diabetes-related traits in Europeans would explain a similar proportion of phenotypic variance in a Pakistani population and could be used in Mendelian randomisation analyses. METHODS: We used data from 2,131 individuals from the Control of Blood Pressure and Risk Attenuation Trial (COBRA) in Karachi, Pakistan. Individuals were aged 40 years or older. RESULTS: Combining information from multiple genetic variants showed that fasting glucose, BMI, triacylglycerol, and systolic and diastolic blood pressure variants explained 2.9%, 0.7%, 5.5%, 1.2% and 1.8% of the variance in those traits respectively. Genetic risk scores of fasting glucose, triacylglycerol, BMI, systolic blood pressure and diastolic blood pressure variants were associated with these traits, with per allele SD effects of 0.057 (95% CI 0.041, 0.074), p=3.44 × 10(-12), 0.130 (95% CI 0.105, 0.155), p=2.9 × 10(-21), 0.04 (95% CI 0.014, 0.072), p=0.004, 0.031 (95% CI 0.016, 0.047), p=7.9 × 10(-5), 0.028 (95% CI 0.015, 0.042), p = 5.5 × 10(-5), respectively. These effects are consistent with those observed in Europeans, except that the effect of triacylglycerol variants in South Asians was slightly lower. Mendelian randomisation provided evidence that genetically influenced, raised triacylglycerol levels do not causally affect type 2 diabetes risk to the extent predicted from observational data (p=0.0003 for difference between observed and instrumental variables correlations). CONCLUSIONS/ INTERPRETATION: Genetic variants identified in Europeans are associated with type 2 diabetes-related traits in Pakistanis, with comparable effect sizes. Larger studies are needed to perform adequately powered Mendelian randomisation and help dissect the relationships between type 2 diabetes-related traits in diverse South Asian subgroups.
Authors: S D Rees; M Islam; M Z I Hydrie; B Chaudhary; S Bellary; S Hashmi; J P O'Hare; S Kumar; D K Sanghera; N Chaturvedi; A H Barnett; A S Shera; M N Weedon; A Basit; T M Frayling; M A Kelly; T H Jafar Journal: Diabet Med Date: 2011-06 Impact factor: 4.359
Authors: Tazeen H Jafar; Andrew S Levey; Fahim H Jafary; Franklin White; Asma Gul; Mohammad H Rahbar; Abdul Q Khan; Andrew Hattersley; Christopher H Schmid; Nish Chaturvedi Journal: J Hypertens Date: 2003-05 Impact factor: 4.844
Authors: Sekar Kathiresan; Olle Melander; Candace Guiducci; Aarti Surti; Noël P Burtt; Mark J Rieder; Gregory M Cooper; Charlotta Roos; Benjamin F Voight; Aki S Havulinna; Björn Wahlstrand; Thomas Hedner; Dolores Corella; E Shyong Tai; Jose M Ordovas; Göran Berglund; Erkki Vartiainen; Pekka Jousilahti; Bo Hedblad; Marja-Riitta Taskinen; Christopher Newton-Cheh; Veikko Salomaa; Leena Peltonen; Leif Groop; David M Altshuler; Marju Orho-Melander Journal: Nat Genet Date: 2008-01-13 Impact factor: 38.330
Authors: Goodarz Danaei; Mariel M Finucane; Yuan Lu; Gitanjali M Singh; Melanie J Cowan; Christopher J Paciorek; John K Lin; Farshad Farzadfar; Young-Ho Khang; Gretchen A Stevens; Mayuree Rao; Mohammed K Ali; Leanne M Riley; Carolyn A Robinson; Majid Ezzati Journal: Lancet Date: 2011-06-24 Impact factor: 79.321
Authors: Tanya M Teslovich; Kiran Musunuru; Albert V Smith; Andrew C Edmondson; Ioannis M Stylianou; Masahiro Koseki; James P Pirruccello; Samuli Ripatti; Daniel I Chasman; Cristen J Willer; Christopher T Johansen; Sigrid W Fouchier; Aaron Isaacs; Gina M Peloso; Maja Barbalic; Sally L Ricketts; Joshua C Bis; Yurii S Aulchenko; Gudmar Thorleifsson; Mary F Feitosa; John Chambers; Marju Orho-Melander; Olle Melander; Toby Johnson; Xiaohui Li; Xiuqing Guo; Mingyao Li; Yoon Shin Cho; Min Jin Go; Young Jin Kim; Jong-Young Lee; Taesung Park; Kyunga Kim; Xueling Sim; Rick Twee-Hee Ong; Damien C Croteau-Chonka; Leslie A Lange; Joshua D Smith; Kijoung Song; Jing Hua Zhao; Xin Yuan; Jian'an Luan; Claudia Lamina; Andreas Ziegler; Weihua Zhang; Robert Y L Zee; Alan F Wright; Jacqueline C M Witteman; James F Wilson; Gonneke Willemsen; H-Erich Wichmann; John B Whitfield; Dawn M Waterworth; Nicholas J Wareham; Gérard Waeber; Peter Vollenweider; Benjamin F Voight; Veronique Vitart; Andre G Uitterlinden; Manuela Uda; Jaakko Tuomilehto; John R Thompson; Toshiko Tanaka; Ida Surakka; Heather M Stringham; Tim D Spector; Nicole Soranzo; Johannes H Smit; Juha Sinisalo; Kaisa Silander; Eric J G Sijbrands; Angelo Scuteri; James Scott; David Schlessinger; Serena Sanna; Veikko Salomaa; Juha Saharinen; Chiara Sabatti; Aimo Ruokonen; Igor Rudan; Lynda M Rose; Robert Roberts; Mark Rieder; Bruce M Psaty; Peter P Pramstaller; Irene Pichler; Markus Perola; Brenda W J H Penninx; Nancy L Pedersen; Cristian Pattaro; Alex N Parker; Guillaume Pare; Ben A Oostra; Christopher J O'Donnell; Markku S Nieminen; Deborah A Nickerson; Grant W Montgomery; Thomas Meitinger; Ruth McPherson; Mark I McCarthy; Wendy McArdle; David Masson; Nicholas G Martin; Fabio Marroni; Massimo Mangino; Patrik K E Magnusson; Gavin Lucas; Robert Luben; Ruth J F Loos; Marja-Liisa Lokki; Guillaume Lettre; Claudia Langenberg; Lenore J Launer; Edward G Lakatta; Reijo Laaksonen; Kirsten O Kyvik; Florian Kronenberg; Inke R König; Kay-Tee Khaw; Jaakko Kaprio; Lee M Kaplan; Asa Johansson; Marjo-Riitta Jarvelin; A Cecile J W Janssens; Erik Ingelsson; Wilmar Igl; G Kees Hovingh; Jouke-Jan Hottenga; Albert Hofman; Andrew A Hicks; Christian Hengstenberg; Iris M Heid; Caroline Hayward; Aki S Havulinna; Nicholas D Hastie; Tamara B Harris; Talin Haritunians; Alistair S Hall; Ulf Gyllensten; Candace Guiducci; Leif C Groop; Elena Gonzalez; Christian Gieger; Nelson B Freimer; Luigi Ferrucci; Jeanette Erdmann; Paul Elliott; Kenechi G Ejebe; Angela Döring; Anna F Dominiczak; Serkalem Demissie; Panagiotis Deloukas; Eco J C de Geus; Ulf de Faire; Gabriel Crawford; Francis S Collins; Yii-der I Chen; Mark J Caulfield; Harry Campbell; Noel P Burtt; Lori L Bonnycastle; Dorret I Boomsma; S Matthijs Boekholdt; Richard N Bergman; Inês Barroso; Stefania Bandinelli; Christie M Ballantyne; Themistocles L Assimes; Thomas Quertermous; David Altshuler; Mark Seielstad; Tien Y Wong; E-Shyong Tai; Alan B Feranil; Christopher W Kuzawa; Linda S Adair; Herman A Taylor; Ingrid B Borecki; Stacey B Gabriel; James G Wilson; Hilma Holm; Unnur Thorsteinsdottir; Vilmundur Gudnason; Ronald M Krauss; Karen L Mohlke; Jose M Ordovas; Patricia B Munroe; Jaspal S Kooner; Alan R Tall; Robert A Hegele; John J P Kastelein; Eric E Schadt; Jerome I Rotter; Eric Boerwinkle; David P Strachan; Vincent Mooser; Kari Stefansson; Muredach P Reilly; Nilesh J Samani; Heribert Schunkert; L Adrienne Cupples; Manjinder S Sandhu; Paul M Ridker; Daniel J Rader; Cornelia M van Duijn; Leena Peltonen; Gonçalo R Abecasis; Michael Boehnke; Sekar Kathiresan Journal: Nature Date: 2010-08-05 Impact factor: 49.962
Authors: N Maneka G De Silva; Rachel M Freathy; Tom M Palmer; Louise A Donnelly; Jian'an Luan; Tom Gaunt; Claudia Langenberg; Michael N Weedon; Beverley Shields; Beatrice A Knight; Kirsten J Ward; Manjinder S Sandhu; Roger M Harbord; Mark I McCarthy; George Davey Smith; Shah Ebrahim; Andrew T Hattersley; Nicholas Wareham; Debbie A Lawlor; Andrew D Morris; Colin N A Palmer; Timothy M Frayling Journal: Diabetes Date: 2011-01-31 Impact factor: 9.461
Authors: Elizabeth K Speliotes; Cristen J Willer; Sonja I Berndt; Keri L Monda; Gudmar Thorleifsson; Anne U Jackson; Hana Lango Allen; Cecilia M Lindgren; Jian'an Luan; Reedik Mägi; Joshua C Randall; Sailaja Vedantam; Thomas W Winkler; Lu Qi; Tsegaselassie Workalemahu; Iris M Heid; Valgerdur Steinthorsdottir; Heather M Stringham; Michael N Weedon; Eleanor Wheeler; Andrew R Wood; Teresa Ferreira; Robert J Weyant; Ayellet V Segrè; Karol Estrada; Liming Liang; James Nemesh; Ju-Hyun Park; Stefan Gustafsson; Tuomas O Kilpeläinen; Jian Yang; Nabila Bouatia-Naji; Tõnu Esko; Mary F Feitosa; Zoltán Kutalik; Massimo Mangino; Soumya Raychaudhuri; Andre Scherag; Albert Vernon Smith; Ryan Welch; Jing Hua Zhao; Katja K Aben; Devin M Absher; Najaf Amin; Anna L Dixon; Eva Fisher; Nicole L Glazer; Michael E Goddard; Nancy L Heard-Costa; Volker Hoesel; Jouke-Jan Hottenga; Asa Johansson; Toby Johnson; Shamika Ketkar; Claudia Lamina; Shengxu Li; Miriam F Moffatt; Richard H Myers; Narisu Narisu; John R B Perry; Marjolein J Peters; Michael Preuss; Samuli Ripatti; Fernando Rivadeneira; Camilla Sandholt; Laura J Scott; Nicholas J Timpson; Jonathan P Tyrer; Sophie van Wingerden; Richard M Watanabe; Charles C White; Fredrik Wiklund; Christina Barlassina; Daniel I Chasman; Matthew N Cooper; John-Olov Jansson; Robert W Lawrence; Niina Pellikka; Inga Prokopenko; Jianxin Shi; Elisabeth Thiering; Helene Alavere; Maria T S Alibrandi; Peter Almgren; Alice M Arnold; Thor Aspelund; Larry D Atwood; Beverley Balkau; Anthony J Balmforth; Amanda J Bennett; Yoav Ben-Shlomo; Richard N Bergman; Sven Bergmann; Heike Biebermann; Alexandra I F Blakemore; Tanja Boes; Lori L Bonnycastle; Stefan R Bornstein; Morris J Brown; Thomas A Buchanan; Fabio Busonero; Harry Campbell; Francesco P Cappuccio; Christine Cavalcanti-Proença; Yii-Der Ida Chen; Chih-Mei Chen; Peter S Chines; Robert Clarke; Lachlan Coin; John Connell; Ian N M Day; Martin den Heijer; Jubao Duan; Shah Ebrahim; Paul Elliott; Roberto Elosua; Gudny Eiriksdottir; Michael R Erdos; Johan G Eriksson; Maurizio F Facheris; Stephan B Felix; Pamela Fischer-Posovszky; Aaron R Folsom; Nele Friedrich; Nelson B Freimer; Mao Fu; Stefan Gaget; Pablo V Gejman; Eco J C Geus; Christian Gieger; Anette P Gjesing; Anuj Goel; Philippe Goyette; Harald Grallert; Jürgen Grässler; Danielle M Greenawalt; Christopher J Groves; Vilmundur Gudnason; Candace Guiducci; Anna-Liisa Hartikainen; Neelam Hassanali; Alistair S Hall; Aki S Havulinna; Caroline Hayward; Andrew C Heath; Christian Hengstenberg; Andrew A Hicks; Anke Hinney; Albert Hofman; Georg Homuth; Jennie Hui; Wilmar Igl; Carlos Iribarren; Bo Isomaa; Kevin B Jacobs; Ivonne Jarick; Elizabeth Jewell; Ulrich John; Torben Jørgensen; Pekka Jousilahti; Antti Jula; Marika Kaakinen; Eero Kajantie; Lee M Kaplan; Sekar Kathiresan; Johannes Kettunen; Leena Kinnunen; Joshua W Knowles; Ivana Kolcic; Inke R König; Seppo Koskinen; Peter Kovacs; Johanna Kuusisto; Peter Kraft; Kirsti Kvaløy; Jaana Laitinen; Olivier Lantieri; Chiara Lanzani; Lenore J Launer; Cecile Lecoeur; Terho Lehtimäki; Guillaume Lettre; Jianjun Liu; Marja-Liisa Lokki; Mattias Lorentzon; Robert N Luben; Barbara Ludwig; Paolo Manunta; Diana Marek; Michel Marre; Nicholas G Martin; Wendy L McArdle; Anne McCarthy; Barbara McKnight; Thomas Meitinger; Olle Melander; David Meyre; Kristian Midthjell; Grant W Montgomery; Mario A Morken; Andrew P Morris; Rosanda Mulic; Julius S Ngwa; Mari Nelis; Matt J Neville; Dale R Nyholt; Christopher J O'Donnell; Stephen O'Rahilly; Ken K Ong; Ben Oostra; Guillaume Paré; Alex N Parker; Markus Perola; Irene Pichler; Kirsi H Pietiläinen; Carl G P Platou; Ozren Polasek; Anneli Pouta; Suzanne Rafelt; Olli Raitakari; Nigel W Rayner; Martin Ridderstråle; Winfried Rief; Aimo Ruokonen; Neil R Robertson; Peter Rzehak; Veikko Salomaa; Alan R Sanders; Manjinder S Sandhu; Serena Sanna; Jouko Saramies; Markku J Savolainen; Susann Scherag; Sabine Schipf; Stefan Schreiber; Heribert Schunkert; Kaisa Silander; Juha Sinisalo; David S Siscovick; Jan H Smit; Nicole Soranzo; Ulla Sovio; Jonathan Stephens; Ida Surakka; Amy J Swift; Mari-Liis Tammesoo; Jean-Claude Tardif; Maris Teder-Laving; Tanya M Teslovich; John R Thompson; Brian Thomson; Anke Tönjes; Tiinamaija Tuomi; Joyce B J van Meurs; Gert-Jan van Ommen; Vincent Vatin; Jorma Viikari; Sophie Visvikis-Siest; Veronique Vitart; Carla I G Vogel; Benjamin F Voight; Lindsay L Waite; Henri Wallaschofski; G Bragi Walters; Elisabeth Widen; Susanna Wiegand; Sarah H Wild; Gonneke Willemsen; Daniel R Witte; Jacqueline C Witteman; Jianfeng Xu; Qunyuan Zhang; Lina Zgaga; Andreas Ziegler; Paavo Zitting; John P Beilby; I Sadaf Farooqi; Johannes Hebebrand; Heikki V Huikuri; Alan L James; Mika Kähönen; Douglas F Levinson; Fabio Macciardi; Markku S Nieminen; Claes Ohlsson; Lyle J Palmer; Paul M Ridker; Michael Stumvoll; Jacques S Beckmann; Heiner Boeing; Eric Boerwinkle; Dorret I Boomsma; Mark J Caulfield; Stephen J Chanock; Francis S Collins; L Adrienne Cupples; George Davey Smith; Jeanette Erdmann; Philippe Froguel; Henrik Grönberg; Ulf Gyllensten; Per Hall; Torben Hansen; Tamara B Harris; Andrew T Hattersley; Richard B Hayes; Joachim Heinrich; Frank B Hu; Kristian Hveem; Thomas Illig; Marjo-Riitta Jarvelin; Jaakko Kaprio; Fredrik Karpe; Kay-Tee Khaw; Lambertus A Kiemeney; Heiko Krude; Markku Laakso; Debbie A Lawlor; Andres Metspalu; Patricia B Munroe; Willem H Ouwehand; Oluf Pedersen; Brenda W Penninx; Annette Peters; Peter P Pramstaller; Thomas Quertermous; Thomas Reinehr; Aila Rissanen; Igor Rudan; Nilesh J Samani; Peter E H Schwarz; Alan R Shuldiner; Timothy D Spector; Jaakko Tuomilehto; Manuela Uda; André Uitterlinden; Timo T Valle; Martin Wabitsch; Gérard Waeber; Nicholas J Wareham; Hugh Watkins; James F Wilson; Alan F Wright; M Carola Zillikens; Nilanjan Chatterjee; Steven A McCarroll; Shaun Purcell; Eric E Schadt; Peter M Visscher; Themistocles L Assimes; Ingrid B Borecki; Panos Deloukas; Caroline S Fox; Leif C Groop; Talin Haritunians; David J Hunter; Robert C Kaplan; Karen L Mohlke; Jeffrey R O'Connell; Leena Peltonen; David Schlessinger; David P Strachan; Cornelia M van Duijn; H-Erich Wichmann; Timothy M Frayling; Unnur Thorsteinsdottir; Gonçalo R Abecasis; Inês Barroso; Michael Boehnke; Kari Stefansson; Kari E North; Mark I McCarthy; Joel N Hirschhorn; Erik Ingelsson; Ruth J F Loos Journal: Nat Genet Date: 2010-10-10 Impact factor: 38.330
Authors: Santosh K Bhargava; Harshpal Singh Sachdev; Caroline H D Fall; Clive Osmond; Ramakrishnan Lakshmy; David J P Barker; Sushant K Dey Biswas; Siddharth Ramji; Dorairaj Prabhakaran; Kolli Srinath Reddy Journal: N Engl J Med Date: 2004-02-26 Impact factor: 91.245
Authors: Rachel M Freathy; Nicholas J Timpson; Debbie A Lawlor; Anneli Pouta; Yoav Ben-Shlomo; Aimo Ruokonen; Shah Ebrahim; Beverley Shields; Eleftheria Zeggini; Michael N Weedon; Cecilia M Lindgren; Hana Lango; David Melzer; Luigi Ferrucci; Giuseppe Paolisso; Matthew J Neville; Fredrik Karpe; Colin N A Palmer; Andrew D Morris; Paul Elliott; Marjo-Riitta Jarvelin; George Davey Smith; Mark I McCarthy; Andrew T Hattersley; Timothy M Frayling Journal: Diabetes Date: 2008-03-17 Impact factor: 9.461
Authors: Mohammed K Ali; M Masood Kadir; Unjali P Gujral; Syeda Sadia Fatima; Romaina Iqbal; Yan V Sun; K M Venkat Narayan; Shafqat Ahmad Journal: Diabetes Obes Metab Date: 2022-07-05 Impact factor: 6.408