Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource

Aims/hypothesis Hyperglycaemia disproportionately affects African-Americans (AfAs). We tested the transferability of 18 single-nucleotide polymorphisms (SNPs) associated with glycaemic traits identified in European ancestry (EuA) populations in 5,984 non-diabetic AfAs. Methods We meta-analysed SNP a...

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Veröffentlicht in:	Diabetologia 2012-11, Vol.55 (11), p.2970-2984
Hauptverfasser:	Liu, C. -T., Ng, M. C. Y., Rybin, D., Adeyemo, A., Bielinski, S. J., Boerwinkle, E., Borecki, I., Cade, B., Chen, Y. D. I., Djousse, L., Fornage, M., Goodarzi, M. O., Grant, S. F. A., Guo, X., Harris, T., Kabagambe, E., Kizer, J. R., Liu, Y., Lunetta, K. L., Mukamal, K., Nettleton, J. A., Pankow, J. S., Patel, S. R., Ramos, E., Rasmussen-Torvik, L., Rich, S. S., Rotimi, C. N., Sarpong, D., Shriner, D., Sims, M., Zmuda, J. M., Redline, S., Kao, W. H., Siscovick, D., Florez, J. C., Rotter, J. I., Dupuis, J., Wilson, J. G., Bowden, D. W., Meigs, J. B.
Format:	Artikel
Sprache:	eng
Schlagworte:	Adult African Americans Aged Aged, 80 and over Atherosclerosis Biological and medical sciences Black or African American - genetics Black or African American - statistics & numerical data Blood Glucose - genetics Databases, Genetic - statistics & numerical data Delta-5 Fatty Acid Desaturase Diabetes Diabetes Mellitus, Type 2 - ethnology Diabetes Mellitus, Type 2 - genetics Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Female Gene Frequency Genetic Predisposition to Disease - ethnology Genetic Predisposition to Disease - genetics Genetics Genomes Glucose Heart Hospitals Human Physiology Humans Hyperglycemia - ethnology Hyperglycemia - genetics Insulin Insulin - genetics Internal Medicine Linkage Disequilibrium Male Medical sciences Medicine Medicine & Public Health Metabolic Diseases Middle Aged Polymorphism, Single Nucleotide - genetics Public health Quantitative Trait Loci - genetics Risk Factors White People - genetics White People - statistics & numerical data Young Adult
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Zusammenfassung:	Aims/hypothesis Hyperglycaemia disproportionately affects African-Americans (AfAs). We tested the transferability of 18 single-nucleotide polymorphisms (SNPs) associated with glycaemic traits identified in European ancestry (EuA) populations in 5,984 non-diabetic AfAs. Methods We meta-analysed SNP associations with fasting glucose (FG) or insulin (FI) in AfAs from five cohorts in the Candidate Gene Association Resource. We: (1) calculated allele frequency differences, variations in linkage disequilibrium (LD), fixation indices (F st s) and integrated haplotype scores (iHSs); (2) tested EuA SNPs in AfAs; and (3) interrogated within ±250 kb around each EuA SNP in AfAs. Results Allele frequency differences ranged from 0.6% to 54%. F st exceeded 0.15 at 6/16 loci, indicating modest population differentiation. All iHSs were
ISSN:	0012-186X 1432-0428 1432-0428
DOI:	10.1007/s00125-012-2656-4