Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

Article

Kooner, Jaspal S., Saleheem, Danish, Sim, Xueling, Sehmi, Joban, Zhang, Weihua, Frossard, Philippe, Been, Latonya F., Chia, Kee-Seng, Dimas, Antigone S., Hassanali, Neelam, Jafar, Tazeen, Jowett, Jeremy B. M., Li, Xinzhong, Radha, Venkatesan, Rees, Simon D., Takeuchi, Fumihiko, Young, Robin and Pinidiyapathirage, Janani M.. 2011. "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci." Nature Genetics. 43 (10), pp. 984-989. https://doi.org/10.1038/ng.921
Article Title

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

ERA Journal ID16629
Article CategoryArticle
AuthorsKooner, Jaspal S. (Author), Saleheem, Danish (Author), Sim, Xueling (Author), Sehmi, Joban (Author), Zhang, Weihua (Author), Frossard, Philippe (Author), Been, Latonya F. (Author), Chia, Kee-Seng (Author), Dimas, Antigone S. (Author), Hassanali, Neelam (Author), Jafar, Tazeen (Author), Jowett, Jeremy B. M. (Author), Li, Xinzhong (Author), Radha, Venkatesan (Author), Rees, Simon D. (Author), Takeuchi, Fumihiko (Author), Young, Robin (Author) and Pinidiyapathirage, Janani M. (Author)
Journal TitleNature Genetics
Journal Citation43 (10), pp. 984-989
Number of Pages17
Year2011
Place of PublicationUnited States
ISSN1061-4036
1546-1718
Digital Object Identifier (DOI)https://doi.org/10.1038/ng.921
Web Address (URL)https://www.nature.com/articles/ng.921
Abstract

We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10 -4 for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10 -8 to P = 1.9 × 10 -11). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10 -4), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.

Keywordsadult; article; clinical article; controlled study; female; gene locus; gene replication; genetic association; genetic identification; genetic predisposition; genetic susceptibility; genome analysis; human; insulin sensitivity; male; non insulin dependent diabetes mellitus; Pakistan; pancreas islet beta cell; population genetics; priority journal; Singapore; single nucleotide polymorphism; South Asia; United Kingdom
Contains Sensitive ContentDoes not contain sensitive content
ANZSRC Field of Research 2020320208. Endocrinology
310509. Genomics
Public Notes

Files associated with this item cannot be displayed due to copyright restrictions.

Institution of OriginUniversity of Southern Queensland
Byline AffiliationsImperial College London, United Kingdom
University of Cambridge, United Kingdom
National University of Singapore
Center for Non-Communicable Diseases, Pakistan
University of Oklahoma, United States
University of Geneva, Switzerland
University of Oxford, United Kingdom
Aga Khan University, Pakistan
Baker Heart and Diabetes Institute, Australia
Madras Diabetes Research Foundation, India
University of Birmingham, United Kingdom
National Center for Global Health and Medicine, Japan
University of Kelaniya, Sri Lanka
Permalink -

https://research.usq.edu.au/item/q390v/genome-wide-association-study-in-individuals-of-south-asian-ancestry-identifies-six-new-type-2-diabetes-susceptibility-loci

Log in to edit
  • 1691
    total views
  • 15
    total downloads
  • 0
    views this month
  • 0
    downloads this month

Export as

Related outputs

Self-assessment tools for assessing cultural competency: a rapid review of literature
Ganeshananthan, Revathy, Xu, Calvin, Brumpton, Kay, Jones, Blake and Pinidiyapathirage, Janani. 2022. "Self-assessment tools for assessing cultural competency: a rapid review of literature." AlterNative: an international journal of indigenous peoples. 18 (4), pp. 586-593. https://doi.org/10.1177/11771801221118114
Exploring the learning environment afforded by an Aboriginal Community Controlled Health service in a rural longitudinal integrated clerkship
Purea, Paul, Brumpton, Kay, Kumar, Koshila and Pinidiyapathirage, Janani. 2022. "Exploring the learning environment afforded by an Aboriginal Community Controlled Health service in a rural longitudinal integrated clerkship." Education for Primary Care. 33 (4), pp. 214-220. https://doi.org/10.1080/14739879.2022.2054371
Physical activity tracking among Sri Lankan adults: findings from a 7-year follow-up of the Ragama Health Study
Pinidiyapathirage, Janani, Kasthuriratne, Anuradhani, Bennie, Jason A., Pathmeswaran, Arunasalam, Biddle, Stuart J. H., de Silva, Hithanadura Janaka, Chackrewarthy, Sureka, Dassanayake, Anuradha S., Ranawaka, Udaya, Kato, Norihiro and Wickremasinghe, Ananda Rajitha. 2021. "Physical activity tracking among Sri Lankan adults: findings from a 7-year follow-up of the Ragama Health Study." Asia-Pacific Journal of Public Health. https://doi.org/10.1177/1010539520971179
Acceptability, technological feasibility and educational value of remotely facilitated simulation based training: A scoping review
Heffernan, Robert, Brumpton, Kay, Randles, David and Pinidiyapathirage, Janani. 2021. "Acceptability, technological feasibility and educational value of remotely facilitated simulation based training: A scoping review." Medical Education Online: an electronic journal. 26 (1), pp. 1-9. https://doi.org/10.1080/10872981.2021.1972506
Epidemiology of melanoma in rural southern Queensland
Kitchener, Scott, Pinidiyapathirage, Janani, Hunter, Keegan, Cochrane, Lynsey, Gederts, Stephanie, Sy, Tim, Watts, Brianna, Murray, Adrienne, Poologasundrum, Manish, Bose, Swaha, Do, Alexander, Hall, John, Reedy, Andrew, Hudson, Lynton and Masel, Matthew. 2019. "Epidemiology of melanoma in rural southern Queensland." Australian Journal of Rural Health. 27 (5), pp. 386-391. https://doi.org/10.1111/ajr.12545
A cross-sectional study of skin cancer secondary prevention in rural general practice
Kitchener, Scott, Pinidiyapathirage, Janani and Hunter, Keegan. 2020. "A cross-sectional study of skin cancer secondary prevention in rural general practice." Australian Journal of General Practice. 49 (7), pp. 447-450. https://doi.org/10.31128/ajgp-05-19-4935
Analysis of agriculture-related life-threatening injuries presenting to emergency departments of rural generalist hospitals in Southern Queensland
Pinidiyapathirage, Janani, Kitchener, Scott, McNamee, Sarah, Wynter, Sacha, Langford, Jack, Doyle, Ashley and McMahon, Andrew. 2018. "Analysis of agriculture-related life-threatening injuries presenting to emergency departments of rural generalist hospitals in Southern Queensland." Emergency Medicine Australasia. 30 (6), pp. 587 - 592. https://doi.org/10.1111/1742-6723.13215
Self-efficacy and planning strategies can improve physical activity levels in women with a recent history of gestational diabetes mellitus
Pinidiyapathirage, Janani, Jayasuriya, Rohan, Cheung, N. Wah and Schwarzer, Ralf. 2018. "Self-efficacy and planning strategies can improve physical activity levels in women with a recent history of gestational diabetes mellitus." Psychology and Health: an international journal. 33 (8), pp. 1062-1077. https://doi.org/10.1080/08870446.2018.1458983
Chronic disease and health risk behaviors among rural agricultural workforce in Queensland
Pinidiyapathirage, Janani, O’Shannessy, Megan, Harte, Jane, Brumby, Susan and Kitchener, Scott. 2018. "Chronic disease and health risk behaviors among rural agricultural workforce in Queensland." Journal of Agromedicine: interface of human health and agriculture. 23 (1), pp. 32-39. https://doi.org/10.1080/1059924X.2017.1387634
A gene expression signature for insulin resistance
Konstantopoulos, Nicky, Foletta, Victoria C., Segal, David H., Shields, Katherine A., Sanigorski, Andrew, Windmill, Kelly, Swinton, Courtney, Connor, Tim, Wanyonyi, Stephen, Dyer, Thomas D., Fahey, Richard P., Watt, Rose A., Curran, Joanne E., Molero, Juan C., Krippner, Guy, Collier, Greg R., James, David E., Blangero, John, Jowett, Jeremy B. and Walder, Ken R.. 2011. "A gene expression signature for insulin resistance." Physiological Genomics. 43 (3), pp. 110-120. https://doi.org/10.1152/physiolgenomics.00115.2010
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
Diagram, Consortium, AGEN-T2D, Consortium, SAT2D, Consortium, MAT2D, Consortium, T2D-GENES, Consortium and Pinidiyapathirage, Janani M.. 2014. "Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility." Nature Genetics. 46 (3), pp. 234-244. https://doi.org/10.1038/ng.2897
Non-alcoholic fatty liver disease in a rural, physically active, low income population in Sri Lanka
Pinidiyapathirage, M. Janani, Dessanayake, Anuradha S., Rajindrajith, Shaman, Kalubowila, Udaya, Kato, Norihiro, Wickremasinghe, A. Rajitha and de Silva, H. Janaka. 2011. "Non-alcoholic fatty liver disease in a rural, physically active, low income population in Sri Lanka." BMC Research Notes. 4, pp. 1-5. https://doi.org/10.1186/1756-0500-4-513
The burden of diabetes mellitus and impaired fasting glucose in an urban population of Sri Lanka
Pinidiyapathirage, M. J., Kasturiratne, A., Ranawake, U. K., Gunasekara, D., Wijekoon, N., Medagoda, K., Perera, S., Takeuchi, F., Kato, N., Warnakulasuriya, T. and Wickremasinghe, A. R.. 2013. "The burden of diabetes mellitus and impaired fasting glucose in an urban population of Sri Lanka." Diabetic Medicine. 30 (3), pp. 326-332. https://doi.org/10.1111/dme.12013
Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
Kato, Norihiro, Loh, Marie, Takeuchi, Fumihiko, Verweij, Niek, Wang, Xu, Zhang, Weihua, Kelly, Tanika N., Saleheen, Danish, Lehne, Benjamin, Leach, Irene Mateo and Pinidiyapathirage, Mohitha J.. 2015. "Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation." Nature Genetics. 47 (11), pp. 1282-1293. https://doi.org/10.1038/ng.3405
Translational research for diabetes self-management in Sri Lanka: a randomized controlled trial
Jayasuriya, R., Pinidiyapathirage, M. J., Jayawardena, R., Kasturiratne, A., de Zoysa, P., Godamunne, P., Gamage, S. and Wickremasinghe, A. R.. 2015. "Translational research for diabetes self-management in Sri Lanka: a randomized controlled trial." Primary Care Diabetes. 9 (5), pp. 338-345. https://doi.org/10.1016/j.pcd.2015.01.014
Epidemiology of hypertension in an urban Sri Lankan population
Kasturiratne, A., Warnakulasuriya, T., Pinidiyapathirage, J., Kato, N., Wickremasinghe, A. and Pathmeswaran, A.. 2011. "Epidemiology of hypertension in an urban Sri Lankan population." Journal of Epidemiology and Community Health. 65, pp. A256-A256. https://doi.org/10.1136/jech.2011.142976i.65
Impact of risk factors for non-fatal acute myocardial infarctions among Sri Lankans
Pinidiyapathirage, J. and Wickremasinghe, A. R.. 2011. "Impact of risk factors for non-fatal acute myocardial infarctions among Sri Lankans." Journal of Epidemiology and Community Health. 65 (Suppl 1), pp. A289-A290. https://doi.org/10.1136/jech.2011.142976j.80
Prevalence and predictors of default with tuberculosis treatment in Sri Lanka
Pinidiyapathirage, Janani, Senaratne, Wijitha and Wickremasinghe, Rajitha. 2008. "Prevalence and predictors of default with tuberculosis treatment in Sri Lanka." Southeast Asian Journal of Tropical Medicine and Public Health. 39 (6), pp. 1076-82.
Activation of the selenoprotein SEPS1 gene expression by pro-inflammatory cytokines in HepG2 cells
Gao, Yuan, Hannan, Nicholas R. F., Wanyonyi, Stephen, Konstantopolous, Nicky, Pagnon, Joanne, Feng, Helen C., Jowett, Jeremy B. M., Kim, Kee-Hong, Walder, Ken and Collier, Greg R.. 2006. "Activation of the selenoprotein SEPS1 gene expression by pro-inflammatory cytokines in HepG2 cells." Cytokine. 33 (5), pp. 246-251. https://doi.org/10.1016/j.cyto.2006.02.005