Mendelian Randomization Analysis Identifies Inverse Causal Relationship between External Eating and Metabolic Phenotypes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Group
2.2. Ethics, Consent, and Permissions
2.3. Anthropometric Measurements and Biochemical Assays
2.4. Eating Behaviour
2.5. Genotyping and Quality Control
2.6. Association Analysis
2.7. Mendelian Randomization
3. Results
3.1. Association Analysis
3.2. Mendelian Randomization
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | All | Men | Women | ||||||
---|---|---|---|---|---|---|---|---|---|
Control (N = 397) | T2D (N = 200) | MetS (N = 279) | Control (N = 201) | T2D (N = 57) | MetS (N = 80) | Control (N = 196) | T2D (N = 143) | MetS (N = 199) | |
Age (years) | 49.65 ± 10.88 | 61.49 ± 9.55 | 57.01 ± 6.97 | 47.24 ± 11.06 | 60.44 ± 9.78 | 56.19 ± 7.50 | 52.12 ± 10.13 | 61.92 ± 9.46 | 57.35 ± 6.73 |
External Eating | 3.33 ± 1.02 | 3.54 ± 0.74 | NA | 3.09 ± 1.07 | 3.35 ± 0.55 | NA | 3.48 ± 0.96 | 3.62 ± 0.79 | NA |
Emotional Eating | 2.64 ± 1.27 | 4.46 ± 1.1 | NA | 2.18 ± 1.3 | 4.24 ± 1.07 | NA | 2.92 ± 1.16 | 4.54 ± 1.1 | NA |
Restraint | 2.86 ± 1.13 | 2.89 ± 0.75 | NA | 2.56 ± 1.28 | 2.83 ± 0.86 | NA | 3.05 ± 0.98 | 2.91 ± 0.71 | NA |
Height (cm) | 173.26 ± 8.21 | 161.7 ± 7.96 | 169.43 ± 7.23 | 176.32 ± 6.25 | 168.79 ± 6.76 | 175.72 ± 4.57 | 163.24 ± 5.41 | 158.87 ± 6.53 | 166.90 ± 6.53 |
Weight (kg) | 79.38 ± 13.09 | 80.97 ± 15.46 | 89.29 ± 5.46 | 82.79 ± 12.12 | 86.82 ± 16.19 | 93.06 ± 5.95 | 68.20 ± 9.46 | 78.64 ± 14.57 | 87.77 ± 4.42 |
BMI (kg/m2) | 27.68 ± 4.5 | 30.92 ± 5.25 | 31.17 ± 2.45 | 27.39 ± 4.26 | 30.41 ± 5.07 | 30.11 ± 2.00 | 27.98 ± 4.73 | 31.12 ± 5.32 | 31.60 ± 2.49 |
Cholesterol (mmol/L) | 5.09 ± 0.64 | 5.43 ± 1.14 | 5.88 ± 0.71 | 5.17 ± 0.55 | 5.57 ± 0.95 | 5.91 ± 0.72 | 5.06 ± 0.67 | 5.38 ± 1.21 | 5.86 ± 0.71 |
Triglycerides (mmol/L) | 1.48 ± 0.6 | 1.68 ± 1.33 | 1.72 ± 0.51 | 1.48 ± 0.61 | 1.93 ± 1.45 | 1.74 ± 0.47 | 1.48 ± 0.60 | 1.58 ± 1.28 | 1.71 ± 0.53 |
HDL (mmol/L) | 1.09 ± 0.37 | 1.2 ± 0.51 | 1.01 ± 0.13 | 1.07 ± 0.34 | 1.27 ± 0.58 | 0.96 ± 0.10 | 1.09 ± 0.38 | 1.17 ± 0.48 | 1.02 ± 0.13 |
LDL (mmol/L) | 2.96 ± 1.08 | 3.05 ± 1.43 | 3.17 ± 0.19 | 3.03 ± 0.98 | 3.18 ± 1.57 | 3.23 ± 0.16 | 2.93 ± 1.11 | 3 ± 1.37 | 3.15 ± 0.20 |
HbA1c (%) | 4.89 ± 0.6 | 7.48 ± 0.99 | 5.28 ± 1.00 | 4.87 ± 0.65 | 7.47 ± 0.94 | 5.12 ± 0.91 | 4.89 ± 0.58 | 7.48 ± 1.01 | 5.34 ± 1.03 |
Fasting Glucose (mmol/L) | 4.88 ± 0.71 | 7.22 ± 1.95 | 5.33 ± 1.38 | 4.79 ± 0.66 | 7.2 ± 2 | 5.19 ± 1.31 | 4.90 ± 0.73 | 7.22 ± 1.93 | 5.38 ± 1.41 |
2 h glucose (mmol/L) | NA | 9.93 ± 2.2 | 6.58 ± 2.42 | NA | 10.17 ± 2.36 | 6.35 ± 2.48 | NA | 9.83 ± 2.13 | 6.67 ± 2.40 |
C-peptide (ng/mL) | 2.31 ± 0.94 | 2.65 ± 5.39 | NA | 2.39 ± 0.87 | 2.18 ± 0.94 | NA | 2.28 | 2.83 ± 6.34 | NA |
Gene | SNP | EA | NEA | EAF | N | Beta/OR | SE | P | PFDR |
---|---|---|---|---|---|---|---|---|---|
Emotional eating | |||||||||
HTR2A | rs6313 | A | G | 0.47 | 286 | 0.36 | 0.11 | 0.001 | 0.041 |
External eating | |||||||||
HTR1D | rs623988 | A | G | 0.29 | 295 | 0.32 | 0.08 | 1.20 × 10−4 | 3.60 × 10−3 |
CDKAL1 | rs9295474 | C | G | 0.64 | 294 | 0.22 | 0.08 | 0.003 | 0.047 |
Type 2 diabetes | |||||||||
CXCR2 | rs2230054 | T | C | 0.44 | 595 | 1.8 | 0.15 | 8.87 × 10−5 | 8.87 × 10−4 |
HTR1F | rs56398417 | C | T | 0.84 | 597 | 2.61 | 0.24 | 5.01 × 10−5 | 7.52 × 10−4 |
NPY2R | rs1047214 | T | C | 0.62 | 400 | 1.82 | 0.17 | 4.56 × 10−4 | 3.42 × 10−3 |
HTR3A | rs1062613 | T | C | 0.19 | 596 | 2.13 | 0.18 | 4.03 × 10−5 | 7.52 × 10−4 |
HTR2A | rs6313 | A | G | 0.47 | 572 | 1.58 | 0.15 | 0.002 | 0.012 |
HTR2C | rs6318 | C | G | 0.09 | 593 | 2.07 | 0.24 | 0.002 | 0.012 |
Metabolic syndrome | |||||||||
CRP | rs2794521 | C | T | 0.21 | 621 | 6.64 | 0.17 | 4.83 × 10−28 | 1.45 × 10−26 |
ADCY3 | rs17799872 | A | G | 0.09 | 641 | 1.90 | 0.19 | 0.001 | 0.004 |
GHRL | rs696217 | T | G | 0.08 | 639 | 2.20 | 0.18 | 2.02 × 10−5 | 1.51 × 10−4 |
CDKAL1 | rs9295474 | G | C | 0.36 | 634 | 1.70 | 0.13 | 4.26 × 10−5 | 2.56 × 10−4 |
BDNF | rs11030107 | G | A | 0.13 | 627 | 1.91 | 0.17 | 1.23 × 10−4 | 0.001 |
CHRM4 | rs2067482 | T | C | 0.08 | 641 | 0.45 | 0.28 | 0.005 | 0.017 |
CHRM1 | rs2067477 | A | C | 0.04 | 637 | 3.33 | 0.26 | 3.80 × 10−6 | 3.80 × 10−5 |
HTR3A | rs1062613 | T | C | 0.19 | 636 | 2.10 | 0.16 | 2.53 × 10−6 | 3.79 × 10−5 |
AKT1 | rs3803300 | A | G | 0.03 | 637 | 2.48 | 0.31 | 0.003 | 0.012 |
Height | |||||||||
HTR2C | rs6318 | C | G | 0.09 | 242 | −3.60 | 0.89 | 7.32 × 10−5 | 0.002 |
Body mass index | |||||||||
ADCY3 | rs17799872 | A | G | 0.09 | 245 | 1.13 | 0.30 | 1.90 × 10−4 | 0.003 |
HTR2C | rs6318 | C | G | 0.09 | 242 | 1.53 | 0.34 | 1.28 × 10−5 | 3.83 × 10−4 |
Waist circumference | |||||||||
HTR2C | rs6318 | C | G | 0.09 | 242 | 4.88 | 1.36 | 3.90 × 10−4 | 0.012 |
Waist–hip ratio | |||||||||
SIRT1 | rs3758391 | C | T | 0.52 | 234 | 0.01 | 0.00 | 0.001 | 0.040 |
Albumin | |||||||||
CDKAL1 | rs9295474 | G | C | 0.36 | 237 | −1.48 | 0.43 | 0.001 | 0.020 |
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Timasheva, Y.; Balkhiyarova, Z.; Avzaletdinova, D.; Morugova, T.; Korytina, G.F.; Nouwen, A.; Prokopenko, I.; Kochetova, O. Mendelian Randomization Analysis Identifies Inverse Causal Relationship between External Eating and Metabolic Phenotypes. Nutrients 2024, 16, 1166. https://doi.org/10.3390/nu16081166
Timasheva Y, Balkhiyarova Z, Avzaletdinova D, Morugova T, Korytina GF, Nouwen A, Prokopenko I, Kochetova O. Mendelian Randomization Analysis Identifies Inverse Causal Relationship between External Eating and Metabolic Phenotypes. Nutrients. 2024; 16(8):1166. https://doi.org/10.3390/nu16081166
Chicago/Turabian StyleTimasheva, Yanina, Zhanna Balkhiyarova, Diana Avzaletdinova, Tatyana Morugova, Gulnaz F. Korytina, Arie Nouwen, Inga Prokopenko, and Olga Kochetova. 2024. "Mendelian Randomization Analysis Identifies Inverse Causal Relationship between External Eating and Metabolic Phenotypes" Nutrients 16, no. 8: 1166. https://doi.org/10.3390/nu16081166