TY - JOUR
T1 - Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels
AU - Qi, Qibin
AU - Menzaghi, Claudia
AU - Smith, Shelly
AU - Liang, Liming
AU - de Rekeneire, Nathalie
AU - Garcia, Melissa E.
AU - Lohman, Kurt K.
AU - Miljkovic, Iva
AU - Strotmeyer, Elsa S.
AU - Cummings, Steve R.
AU - Kanaya, Alka M.
AU - Tylavsky, Frances A.
AU - Satterfield, Suzanne
AU - Ding, Jingzhong
AU - Rimm, Eric B.
AU - Trischitta, Vincenzo
AU - Hu, Frank B.
AU - Liu, Yongmei
AU - Qi, Lu
N1 - Funding Information:
This research in the NHS and HPFS is supported by grants DK091718, HL071981, U01HG004399, HL71981, HL073 168, U01HG004399, DK58845 and DK46200. L.Q. is a recipient of the American Heart Association Scientist Development Award (0730094N). The genotyping of the HPFS and NHS CHD GWAS was supported by an unrestricted grant from Merck Research Laboratories, North Wales, PA, USA. This research in the Health ABC was supported by NIH/NIA contracts N01AG62101, N01AG62103 and N01AG62106. The genome-wide association study in the Health ABC was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences, and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Part of the research described in this paper was supported by Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST 2006, an Italian Ministry of Health grant (RC2011 and RC2012), an EFSD/ Pfizer grant (C.M.).
PY - 2012/11
Y1 - 2012/11
N2 - Resistin is a polypeptide hormone that was reported to be associated with insulin resistance, inflammation and risk of type 2 diabetes and cardiovascular disease. We conducted a genome-wide association (GWA) study on circulating resistin levels in individuals of European ancestry drawn from the two independent studies: the Nurses' Health Study (n = 1590) and the Health, Aging and Body Composition Study (n = 1658). Single-nucleotide polymorphisms (SNPs) identified in the GWA analysis were replicated in an independent cohort of Europeans: the Gargano Family Study (n = 659). We confirmed the association with a previously known locus, the RETN gene (19p13.2), and identified two novel loci near the TYW3/CRYZ gene (1p31) and the NDST4 gene (4q25), associated with resistin levels at a genome-wide significant level, best represented by SNP rs3931020 (P = 6.37 × 10-12) and SNP rs13144478 (P = 6.19 × 10-18), respectively. Gene expression quantitative trait loci analyses showed a significant cis association between the SNP rs3931020 and CRYZ gene expression levels (P = 3.68 × 10-7). We also found that both of these two SNPs were significantly associated with resistin gene (RETN) mRNA levels in white blood cells from 68 subjects with type 2 diabetes (both P = 0.02). In addition, the resistin-rising allele of the TYW3/CRYZ SNP rs3931020, but not the NDST4 SNP rs13144478, showed a consistent association with increased coronary heart disease risk [odds ratio = 1.18 (95% CI, 1.03-1.34); P = 0.01]. Our results suggest that genetic variants in TYW3/CRYZ and NDST4 loci may be involved in the regulation of circulating resistin levels. More studies are needed to verify the associations of the SNP rs13144478 with NDST4 gene expression and resistin-related disease.
AB - Resistin is a polypeptide hormone that was reported to be associated with insulin resistance, inflammation and risk of type 2 diabetes and cardiovascular disease. We conducted a genome-wide association (GWA) study on circulating resistin levels in individuals of European ancestry drawn from the two independent studies: the Nurses' Health Study (n = 1590) and the Health, Aging and Body Composition Study (n = 1658). Single-nucleotide polymorphisms (SNPs) identified in the GWA analysis were replicated in an independent cohort of Europeans: the Gargano Family Study (n = 659). We confirmed the association with a previously known locus, the RETN gene (19p13.2), and identified two novel loci near the TYW3/CRYZ gene (1p31) and the NDST4 gene (4q25), associated with resistin levels at a genome-wide significant level, best represented by SNP rs3931020 (P = 6.37 × 10-12) and SNP rs13144478 (P = 6.19 × 10-18), respectively. Gene expression quantitative trait loci analyses showed a significant cis association between the SNP rs3931020 and CRYZ gene expression levels (P = 3.68 × 10-7). We also found that both of these two SNPs were significantly associated with resistin gene (RETN) mRNA levels in white blood cells from 68 subjects with type 2 diabetes (both P = 0.02). In addition, the resistin-rising allele of the TYW3/CRYZ SNP rs3931020, but not the NDST4 SNP rs13144478, showed a consistent association with increased coronary heart disease risk [odds ratio = 1.18 (95% CI, 1.03-1.34); P = 0.01]. Our results suggest that genetic variants in TYW3/CRYZ and NDST4 loci may be involved in the regulation of circulating resistin levels. More studies are needed to verify the associations of the SNP rs13144478 with NDST4 gene expression and resistin-related disease.
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U2 - 10.1093/hmg/dds300
DO - 10.1093/hmg/dds300
M3 - Article
C2 - 22843503
AN - SCOPUS:84867793742
SN - 0964-6906
VL - 21
SP - 4774
EP - 4780
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 21
M1 - dds300
ER -
