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Polymorphisms in the ANKS1B gene are associated with cancer, obesity and type 2 diabetes

Ke-Sheng Wang Xuefeng Liu Daniel Owusu Yue Pan Changchun Xie

*Corresponding author: Ke-Sheng Wang wangk@etsu.edu


Obesity and type 2 diabetes (T2D) are comorbidities with cancer which may be partially due to shared genetic variants. Genetic variants in the ankyrin repeat and sterile alpha motif domain containing 1B (ANKS1B) gene may play a role in cancer, adiposity, body mass index (BMI), and body weight. However, few studies focused on the associations of ANKS1B with obesity and T2D. We examined genetic associations of 272 single nucleotide polymorphisms (SNPs) within the ANKS1B with the cancer (any diagnosed cancer omitting minor skin cancer), obesity and T2D using the Marshfield sample (716 individuals with cancers, 1442 individuals with obesity, and 878 individuals with T2D). The Health Aging and Body Composition (Health ABC) sample (305 obese and 1336 controls) was used for replication. Multiple logistic regression analysis was performed using the PLINK software. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. We identified 25 SNPs within the ANKS1B gene associated with cancer, 34 SNPs associated with obesity, and 12 SNPs associated with T2D (p < 0.05). The most significant SNPs associated with cancer, T2D, and obesity were rs2373013 (p = 2.21 × 10-4), rs10860548 (p = 1.92 × 10-3), and rs7139028 (p = 1.94 × 10-6), respectively. Interestingly, rs3759214 was identified for both cancer and T2D (p = 0.0161 and 0.044, respectively). Furthermore, seven SNPs were associated with both cancer and obesity (top SNP rs2372719 with p = 0.0161 and 0.0206, respectively); six SNPs were associated with both T2D and obesity (top SNP rs7139028 with p = 0.0231 and 1.94 × 10-6, respectively). In the Health ABC sample, 18 SNPs were associated with obesity, 5 of which were associated with cancer in the Marshfield sample. In addition, three SNPs (rs616804, rs7295102, and rs201421) were associated with obesity in meta-analysis using both samples. These findings provide evidence of common genetic variants in the ANKS1B gene influencing the risk of cancer, obesity, and T2D and will serve as a resource for replication in other populations.

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