School of Medicine Publications and Presentations
Document Type
Article
Publication Date
5-15-2016
Abstract
To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci.
Recommended Citation
Horikoshi, M., Pasquali, L., Wiltshire, S., Huyghe, J. R., Mahajan, A., Asimit, J. L., Ferreira, T., Locke, A. E., Robertson, N. R., Wang, X., Sim, X., Fujita, H., Hara, K., Young, R., Zhang, W., Choi, S., Chen, H., Kaur, I., Takeuchi, F., Fontanillas, P., … T2D-GENES Consortium (2016). Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms. Human molecular genetics, 25(10), 2070–2081. https://doi.org/10.1093/hmg/ddw048
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
First Page
2070
Last Page
2081
Publication Title
Human Molecular Genetics
DOI
10.1093/hmg/ddw048
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
© The Author 2016. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.