Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels

Qibin Qi, Claudia Menzaghi, Shelly Smith, Liming Liang, Nathalie de Rekeneire, Melissa E. Garcia, Kurt K. Lohman, Iva Miljkovic, Elsa S. Strotmeyer, Steve R. Cummings, Alka M. Kanaya, Frances A. Tylavsky, Suzanne Satterfield, Jingzhong Ding, Eric B. Rimm, Vincenzo Trischitta, Frank B. Hu, Yongmei Liu, Lu Qi

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article numberdds300
Pages (from-to)4774-4780
Number of pages7
JournalHuman Molecular Genetics
Volume21
Issue number21
DOIs
Publication statusPublished - Nov 2012

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Resistin
Genome-Wide Association Study
Single Nucleotide Polymorphism
Genes
Gene Expression
Type 2 Diabetes Mellitus
Odds Ratio
Peptide Hormones
Quantitative Trait Loci
Health
Body Composition
Coronary Disease
Insulin Resistance
Leukocytes
Cardiovascular Diseases
Alleles
Nurses
Genome
Inflammation
Messenger RNA

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels. / Qi, Qibin; Menzaghi, Claudia; Smith, Shelly; Liang, Liming; de Rekeneire, Nathalie; Garcia, Melissa E.; Lohman, Kurt K.; Miljkovic, Iva; Strotmeyer, Elsa S.; Cummings, Steve R.; Kanaya, Alka M.; Tylavsky, Frances A.; Satterfield, Suzanne; Ding, Jingzhong; Rimm, Eric B.; Trischitta, Vincenzo; Hu, Frank B.; Liu, Yongmei; Qi, Lu.

In: Human Molecular Genetics, Vol. 21, No. 21, dds300, 11.2012, p. 4774-4780.

Research output: Contribution to journalArticle

Qi, Q, Menzaghi, C, Smith, S, Liang, L, de Rekeneire, N, Garcia, ME, Lohman, KK, Miljkovic, I, Strotmeyer, ES, Cummings, SR, Kanaya, AM, Tylavsky, FA, Satterfield, S, Ding, J, Rimm, EB, Trischitta, V, Hu, FB, Liu, Y & Qi, L 2012, 'Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels', Human Molecular Genetics, vol. 21, no. 21, dds300, pp. 4774-4780. https://doi.org/10.1093/hmg/dds300
Qi, Qibin ; Menzaghi, Claudia ; Smith, Shelly ; Liang, Liming ; de Rekeneire, Nathalie ; Garcia, Melissa E. ; Lohman, Kurt K. ; Miljkovic, Iva ; Strotmeyer, Elsa S. ; Cummings, Steve R. ; Kanaya, Alka M. ; Tylavsky, Frances A. ; Satterfield, Suzanne ; Ding, Jingzhong ; Rimm, Eric B. ; Trischitta, Vincenzo ; Hu, Frank B. ; Liu, Yongmei ; Qi, Lu. / Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels. In: Human Molecular Genetics. 2012 ; Vol. 21, No. 21. pp. 4774-4780.
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AU - Qi, Qibin

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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

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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.

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