| Title |
GWAS identifies population-specific new regulatory variants in FUT6 associated with plasma B12 concentrations in Indians
|
|---|---|
| Published in |
Human Molecular Genetics, February 2017
|
| DOI | 10.1093/hmg/ddx071 |
| Pubmed ID | |
| Authors |
Suraj S. Nongmaithem, Charudatta V. Joglekar, Ghattu V. Krishnaveni, Sirazul A. Sahariah, Meraj Ahmad, Swetha Ramachandran, Meera Gandhi, Harsha Chopra, Anand Pandit, Ramesh D. Potdar, Caroline H.D. Fall, Chittaranjan S. Yajnik, Giriraj R. Chandak |
| Abstract |
Vitamin B12 is an important cofactor in one-carbon metabolism whose dysregulation is associated with various clinical conditions. Indians have a high prevalence of B12 deficiency but little is known about the genetic determinants of circulating B12 concentrations in Indians. We performed a genome-wide association study in 1001 healthy participants in the Pune Maternal Nutrition Study (PMNS), replication studies in 3418 individuals from other Indian cohorts and by meta-analysis identified new variants, rs3760775 (p = 1.2x10-23) and rs78060698 (p = 8.3x10-17) in FUT6 to be associated with circulating B12 concentrations. Although in-silico analysis replicated both variants in Europeans, differences in the effect allele frequency, effect size and the linkage disequilibrium structure of credible set variants with the reported variants suggest population-specific characteristics in this region. We replicated previously reported variants rs602662, rs601338 in FUT2, rs3760776, rs708686 in FUT6, rs34324219 in TCN1 (all p < 5x10-8), rs1131603 in TCN2 (p = 3.4x10-5), rs12780845 in CUBN (p = 3.0x10-3) and rs2270655 in MMAA (p = 2.0x10-3). Circulating B12 concentrations in the PMNS and Parthenon study showed a significant decline with increasing age (p < 0.001), however, the genetic contribution to B12 concentrations remained constant. Luciferase reporter and electrophoretic-mobility shift assay for the FUT6 variant rs78060698 using HepG2 cell line demonstrated strong allele-specific promoter and enhancer activity and differential binding of HNF4α, a key regulator of expression of various fucosyltransferases. Hence, the rs78060698 variant, through regulation of fucosylation may control intestinal host-microbial interaction which could influence B12 concentrations. Our results suggest that in addition to established genetic variants, population-specific variants are important in determining plasma B12 concentrations. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 81 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 81 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 16 | 20% |
| Student > Ph. D. Student | 16 | 20% |
| Student > Bachelor | 14 | 17% |
| Researcher | 7 | 9% |
| Other | 5 | 6% |
| Other | 10 | 12% |
| Unknown | 13 | 16% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 22 | 27% |
| Biochemistry, Genetics and Molecular Biology | 14 | 17% |
| Agricultural and Biological Sciences | 12 | 15% |
| Nursing and Health Professions | 6 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 2% |
| Other | 7 | 9% |
| Unknown | 18 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 March 2017.
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#14,928,316
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Outputs from Human Molecular Genetics
#6,524
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Outputs of similar age from Human Molecular Genetics
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