ArticleMetabolism: clinical and experimental2014
Genome-wide association study identifies common loci influencing circulating glycated hemoglobin (HbA1c) levels in non-diabetic subjects: the Long Life Family Study (LLFS).
Article in Metabolism: clinical and experimental, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.PLoS genetics · 2019Pooled it
- Pooled it
- Genome-wide meta-analysis in Japanese populations identifies novel variants at the TMC6-TMC8 and SIX3-SIX2 loci associated with HbAScientific reports · 2017Pooled it
- Evidence of a novel gene locusPhysiological genomics · 2025Article
- A Novel GenebioRxiv : the preprint server for biology · 2024Article
- A genome-wide association study identifies genetic determinants of hemoglobin glycation index with implications across sex and ethnicity.Frontiers in endocrinology · 2024Article
- Variants influencing age at diagnosis of HNF1A-MODY.Molecular medicine (Cambridge, Mass.) · 2022Article
- NIA Long Life Family Study: Objectives, Design, and Heritability of Cross-Sectional and Longitudinal Phenotypes.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Genetic Signatures of Glucose Homeostasis: Synergistic Interplay With Long-Term Exposure to Cigarette Smoking in Development of Primary Colorectal Cancer Among African American Women.Clinical and translational gastroenterology · 2021Article
- Genetic associations for two biological age measures point to distinct aging phenotypes.Aging cell · 2021Article
- Determination of individual type 2 diabetes risk profile in the North East Indian population & its association with anthropometric parameters.The Indian journal of medical research · 2019Article
- Genetic Variants Associated With Obesity and Insulin Resistance in Hispanic Boys With Nonalcoholic Fatty Liver Disease.Journal of pediatric gastroenterology and nutrition · 2018Article
- Relationship between soluble receptor for advanced glycation end products (sRAGE), body composition and fat distribution in healthy women.European journal of nutrition · 2017Article
- Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases.Science (New York, N.Y.) · 2016Article
- Are There Clinical Implications of Racial Differences in HbA1c? A Difference, to Be a Difference, Must Make a Difference.Diabetes care · 2016Article
- Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study.BMC geriatrics · 2016Article
- Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk.PloS one · 2015Article
- Adjusting family relatedness in data-driven burden test of rare variants.Genetic epidemiology · 2014Article
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Authors and funding
20 authors at 9 institutions in 2 countries.
Funding
Abstract
objectiveGlycated hemoglobin (HbA1c) is a stable index of chronic glycemic status and hyperglycemia associated with progressive development of insulin resistance and frank diabetes. It is also associated with premature aging and increased mortality. To uncover novel loci for HbA1c that are associated with healthy aging, we conducted a genome-wide association study (GWAS) using non-diabetic participants in the Long Life Family Study (LLFS), a study with familial clustering of exceptional longevity in the US and Denmark.
methodsA total of 4088 non-diabetic subjects from the LLFS were used for GWAS discoveries, and a total of 8231 non-diabetic subjects from the Atherosclerosis Risk in Communities Study (ARIC, in the MAGIC Consortium) and the Health, Aging, and Body Composition Study (HABC) were used for GWAS replications. HbA1c was adjusted for age, sex, centers, 20 principal components, without and with BMI. A linear mixed effects model was used for association testing.
resultsTwo known loci at GCK rs730497 (or rs2908282) and HK1 rs17476364 were confirmed (p<5e-8). Of 25 suggestive (5e-8<p<1e-5) loci, one known (G6PC2 rs560887, replication p=5e-5) and one novel (OR10R3P/SPTA1- rs12041363, replication p=1e-17) loci were replicated (p<0.0019). Similar findings resulted when HbA1c was further adjusted for BMI. Further validations are crucial for the remaining suggestive loci including the emerged variant near OR10R3P/SPTA1.
conclusionsThe analysis reconfirmed two known GWAS loci (GCK, HK1) and identified 25 suggestive loci including one reconfirmed variant in G6PC2 and one replicated variant near OR10R3P/SPTA1. Future focused survey of sequence elements containing mainly functional and regulatory variants may yield additional findings.
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