Interactions between multiple serum metals and genetic variants for type 2 diabetes risk: A prospective Chinese cohort study
Abstract Background: Relationships between metal exposure and type 2 diabetes (T2D) varied depending on the metal involved. In addition, there is limited epidemiological evidence on the interaction between metal exposure and genetic risk for T2D. Therefore, we analyzed the interaction effect of serum concentrations of multiple metals and genetic variants on T2D incidence in the general population. Methods: A prospective cohort study with 14 years of follow-up was performed with 4507 participants without noncommunicable diseases in the Wuxi Non-Communicable Diseases (Wuxi NCDs) cohort. Twenty-one metals were measured using inductively coupled plasma‒mass spectrometry (ICP-MS). Eighty T2D-associated single nucleotide polymorphisms (SNPs) identified by GWAS were genotyped. Two polygenic risk score (PRS) models based on 46 SNPs from East Asians and 80 SNPs from Europeans and East Asians were constructed. A Cox regression model was used to explore the associations of serum metals and their interaction effects with T2D. Results: Of the 4507 participants, 350 were newly diagnosed with T2D during the 14-year follow-up. After adjusting for age, smoking status, body mass index (BMI), hip circumference (HC), waist circumference (WC), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), fasting blood glucose (FBG), triglyceride (TG), and blood pressure (BP), serum vanadium (V), chromium (Cr), manganese (Mn), molybdenum (Mo), barium (Ba) and lead (Pb) levels were correlated with decreased T2D risk, while zinc (Zn) levels were correlated with elevated T2D risk (P<0.05). Mo, Ba and Pb showed interactive effects with the combined PRS derived from 80 SNPs and with the PRS specific for east Asians derived from 46 SNPs. Regardless of race, the risk of T2D increased with decreasing Mo, Ba, and Pb concentrations and increasing PRS. At the lowest Mo, Ba and Pb levels and the highest PRS derived from 80 SNPs, the risk of T2D was 4.18 times greater (HR=4.18, P value for interaction=1.14×10-4 for Mo and PRS), 1.77 times greater (HR=1.77, P value for interaction=0.012 for Ba and PRS) and 14.02 times greater (HR=14.02, P value for interaction=0.009 for Pb and PRS) than that of the reference group, respectively. Conclusions: Our results showed that V, Cr, Mn, Mo, Ba and Pb were negatively correlated with T2D, while Zn was positively correlated. There was an interaction effect between serum Mo, Ba, and Pb levels and PRS on the occurrence of T2D..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 13. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shen, Bohui [VerfasserIn] |
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Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-4010988/v1 |
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XRA04290627X |
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| 520 | |a Abstract Background: Relationships between metal exposure and type 2 diabetes (T2D) varied depending on the metal involved. In addition, there is limited epidemiological evidence on the interaction between metal exposure and genetic risk for T2D. Therefore, we analyzed the interaction effect of serum concentrations of multiple metals and genetic variants on T2D incidence in the general population. Methods: A prospective cohort study with 14 years of follow-up was performed with 4507 participants without noncommunicable diseases in the Wuxi Non-Communicable Diseases (Wuxi NCDs) cohort. Twenty-one metals were measured using inductively coupled plasma‒mass spectrometry (ICP-MS). Eighty T2D-associated single nucleotide polymorphisms (SNPs) identified by GWAS were genotyped. Two polygenic risk score (PRS) models based on 46 SNPs from East Asians and 80 SNPs from Europeans and East Asians were constructed. A Cox regression model was used to explore the associations of serum metals and their interaction effects with T2D. Results: Of the 4507 participants, 350 were newly diagnosed with T2D during the 14-year follow-up. After adjusting for age, smoking status, body mass index (BMI), hip circumference (HC), waist circumference (WC), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), fasting blood glucose (FBG), triglyceride (TG), and blood pressure (BP), serum vanadium (V), chromium (Cr), manganese (Mn), molybdenum (Mo), barium (Ba) and lead (Pb) levels were correlated with decreased T2D risk, while zinc (Zn) levels were correlated with elevated T2D risk (P<0.05). Mo, Ba and Pb showed interactive effects with the combined PRS derived from 80 SNPs and with the PRS specific for east Asians derived from 46 SNPs. Regardless of race, the risk of T2D increased with decreasing Mo, Ba, and Pb concentrations and increasing PRS. At the lowest Mo, Ba and Pb levels and the highest PRS derived from 80 SNPs, the risk of T2D was 4.18 times greater (HR=4.18, P value for interaction=1.14×10-4 for Mo and PRS), 1.77 times greater (HR=1.77, P value for interaction=0.012 for Ba and PRS) and 14.02 times greater (HR=14.02, P value for interaction=0.009 for Pb and PRS) than that of the reference group, respectively. Conclusions: Our results showed that V, Cr, Mn, Mo, Ba and Pb were negatively correlated with T2D, while Zn was positively correlated. There was an interaction effect between serum Mo, Ba, and Pb levels and PRS on the occurrence of T2D. | ||
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| 700 | 1 | |a Guo, Xiangxin |4 aut | |
| 700 | 1 | |a Shen, Qian |4 aut | |
| 700 | 1 | |a Yang, Man |4 aut | |
| 700 | 1 | |a Liu, Yongchao |4 aut | |
| 700 | 1 | |a Chen, Hai |4 aut | |
| 700 | 1 | |a Yang, Zhijie |4 aut | |
| 700 | 1 | |a Liu, Yaqi |4 aut | |
| 700 | 1 | |a Zhu, Xiaowei |4 aut | |
| 700 | 1 | |a Wang, Lu |4 aut | |
| 700 | 1 | |a Jin, Guangfu |4 aut | |
| 700 | 1 | |a Qian, Yun |4 aut | |
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