Journal
ANNALS OF HUMAN GENETICS
Volume 78, Issue 1, Pages 23-32Publisher
WILEY
DOI: 10.1111/ahg.12044
Keywords
Type 2 diabetes; PPAR; PGC1
Categories
Funding
- United States National Institutes of Health (NIH) [KO1 DK082639, R01CA124558, R01CA64277, R37CA70867, R01CA90899, R01CA100374]
- NIH [R01 CA118229, R01CA92585]
- Allen Foundation Fund
- Vanderbilt CTSA grant from the National Center for Research Resources (NCRR)/NIH [1 UL1 RR024975]
- Department of Defense [BC050791, DK58845, HG004399]
- Vanderbilt-Ingram Cancer Center [P30 CA68485]
- [R01CA122756]
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We used a two-stage study design to evaluate whether variations in the peroxisome proliferator-activated receptors (PPAR) and the PPAR gamma co-activator 1 (PGC1) gene families (PPARA, PPARG, PPARD, PPARGC1A, and PPARGC1B) are associated with type 2 diabetes (T2D) risk. Stage I used data from a genome-wide association study (GWAS) from Shanghai, China (1019 T2D cases and 1709 controls) and from a meta-analysis of data from the Asian Genetic Epidemiology Network for T2D (AGEN-T2D). Criteria for selection of single nucleotide polymorphisms (SNPs) for stage II were: (1) P < 0.05 in single marker analysis in Shanghai GWAS and P < 0.05 in the meta-analysis or (2) P < 10(-3) in the meta-analysis alone and (3) minor allele frequency 0.10. Nine SNPs from the PGC1 family were assessed in stage II (an independent set of middle-aged men and women from Shanghai with 1700 T2D cases and 1647 controls). One SNP in PPARGC1B, rs251464, was replicated in stage II (OR = 0.87; 95% CI: 0.77-0.99). Gene-body mass index (BMI) and gene-exercise interactions and T2D risk were evaluated in a combined dataset (Shanghai GWAS and stage II data: 2719 cases and 3356 controls). One SNP in PPARGC1A, rs12640088, had a significant interaction with BMI. No interactions between the PPARGC1B gene and BMI or exercise were observed.
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