Journal article
Trans-ethnic meta-analysis and functional annotation illuminates the genetic architecture of fasting glucose and insulin
- Abstract:
- Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Publisher copy:
- 10.1016/j.ajhg.2016.05.006
Authors
- Publisher:
- Elsevier
- Journal:
- American Journal of Human Genetics More from this journal
- Volume:
- 99
- Issue:
- 1
- Pages:
- 56-75
- Publication date:
- 2016-07-16
- Acceptance date:
- 2016-05-02
- DOI:
- EISSN:
-
1537-6605
- ISSN:
-
0002-9297
- Pmid:
-
27321945
- Language:
-
English
- Keywords:
- Pubs id:
-
pubs:630164
- UUID:
-
uuid:34aa6676-b3ba-4746-afd1-fa6129c3e6d7
- Local pid:
-
pubs:630164
- Source identifiers:
-
630164
- Deposit date:
-
2016-09-06
- ARK identifier:
Terms of use
- Copyright holder:
- © 2016 American Society of Human Genetics
- Copyright date:
- 2016
- Notes:
- This is the author accepted manuscript following peer review] version of the article. The final version is available online from Elsevier at: 10.1016/j.ajhg.2016.05.006
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