Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus
Abstract
:1. Introduction
2. Results
2.1. Overview of Behavior-Related Phenotypes
2.2. Estimation of Relative Expected Heritability by LDAK
2.3. Estimation of Relative Expected Heritability by LDAK-Thin
2.4. Biological Function Analysis
2.5. Screening of Hub Genes
2.6. Significant Upregulation of RPTOR
3. Discussion
4. Materials and Methods
4.1. Identification for Candidate Environmental Phenotypes Associated with Type 2 Diabetes
4.2. The Data Source
4.3. LDAK Model
4.4. LDAK-Thin Model
4.5. Model Implementation
4.6. Estimation and Comparison of Expected Heritability
4.7. Biological Function Analysis
4.7.1. Functional Annotation
4.7.2. KEGG Pathway Enrichment Analysis
4.7.3. Protein Interaction Network Analysis
4.7.4. Screening of Hub Genes
4.7.5. Expression Analysis of Hub Gene in Blood Samples
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Factors | PMID | Year | Case | Control | Unit |
---|---|---|---|---|---|
Alcohol consumption | 30643251 | 2019 | 941,280 | NA | Drinks/week |
Coffee consumption | 31046077 | 2019 | 375,833 | NA | NA |
Caffeine intake | 21490707 | 2011 | 47,341 | NA | mg/d |
Breakfast skipping | 31190057 | 2019 | 193,860 | NA | NA |
Lifetime smoking index | 31689377 | 2019 | 462,690 | NA | SD |
Daytime napping | 31409809 | 2019 | 452,071 | NA | Events |
Sleep duration | 30846698 | 2019 | 446,118 | NA | Hours/d |
Short sleep | 30846698 | 2019 | 106,192 | 305,742 | Events |
Long sleep | 30846698 | 2019 | 34,184 | 305,742 | Events |
Insomnia | 30804565 | 2019 | 397,972 | 933,038 | Events |
Morningness | 30696823 | 2019 | 372,765 | 278,530 | Events |
Restless leg syndrome | 29029846 | 2017 | 15,126 | 95,725 | Events |
Moderate to vigorous physical activity | 29899525 | 2018 | 377,234 | NA | SD |
Strenuous sports | 29899525 | 2018 | 124,842 | 225,650 | ≥2–3 vs. 0 day/weeks |
Vigorous physical | 29899525 | 2018 | 98,060 | 162,995 | ≥3 vs. 0 day/weeks |
Accelerometer | 29899525 | 2018 | 91,084 | NA | NA |
Educational attainment | 30038396 | 2018 | 1,131,881 | NA | SD |
Behavior-Related Phenotypes | Variants Reported in Literature | Variants in Tagging File | Valid Variants Analyzed | MAF (s.d.) | EAF (s.d.) |
---|---|---|---|---|---|
Type 2 diabetes | 403 | 363 | 363 | 0.25(0.14) | 0.48(0.28) |
Educational attainment | 1272 | 1263 | 1624 | 0.27(0.14) | 0.46(0.26) |
Lifetime smoking index | 126 | 126 | 489 | 0.31(0.12) | 0.49(0.22) |
Alcohol consumption | 99 | 98 | 460 | 0.27(0.14) | 0.44(0.27) |
Coffee consumption | 15 | 14 | 376 | 0.25(0.14) | 0.39(0.26) |
Breakfast skipping | 6 | 6 | 369 | 0.21(0.08) | 0.50(0.31) |
Caffeine intake | 2 | 2 | 365 | 0.34(0.07) | 0.34(0.04) |
Morningness | 351 | 342 | 703 | 0.30(0.13) | 0.46(0.23) |
Insomnia | 248 | 244 | 606 | 0.30(0.13) | 0.49(0.24) |
Sleep duration | 78 | 77 | 440 | 0.29(0.13) | 0.52(0.25) |
Daytime napping | 37 | 36 | 399 | 0.34(0.12) | 0.57(0.20) |
Short sleep | 27 | 26 | 389 | 0.29(0.11) | 0.50(0.25) |
Restless leg syndrome | 20 | 20 | 383 | 0.28(0.13) | 0.51(0.27) |
Moderate to vigorous physical activity | 9 | 9 | 371 | 0.26(0.16) | 0.47(0.29) |
Strenuous sports | 6 | 6 | 369 | 0.26(0.16) | 0.53(0.28) |
Vigorous physical | 5 | 5 | 368 | 0.34(0.14) | 0.34(0.14) |
Accelerometer | 2 | 2 | 365 | 0.29(0.03) | 0.72(0.10) |
Total | 2674 | 2607 | 2607 | 0.28(0.14) | 0.47(0.25) |
Phenotypes | Expected Heritability | |||||
---|---|---|---|---|---|---|
Estimation | Simulation (s.d.) | AHPV | RHPV | |||
Type 2 diabetes | 3.2 | - | 0.01 | - | - | - |
Caffeine intake * | 3.3 | 3.3(0.0) | 0.01 | 0.04 | 2.43 | 4.51 |
Alcohol consumption * | 5.2 | 4.3(0.3) | 0.01 | 0.02 | 37.45 | 2.24 |
Breakfast skipping | 3.4 | 3.3(0.1) | 0.01 | 0.02 | 4.06 | 2.56 |
Coffee consumption | 3.5 | 3.4(0.1) | 0.01 | 0.02 | 7.73 | 2.34 |
Strenuous sports | 3.3 | 3.3(0.1) | 0.01 | 0.02 | 3.26 | 2.04 |
Moderate to vigorous physical activity | 3.3 | 3.3(0.1) | 0.01 | 0.01 | 2.33 | 1.08 |
Educational attainment | 13.7 | 16.2(1.2) | 0.01 | 0.01 | 76.43 | 0.93 |
Insomnia | 5.2 | 5.7(0.4) | 0.01 | 0.01 | 37.45 | 0.89 |
Morningness | 4.8 | 6.6(0.6) | 0.01 | 0.00 | 32.01 | 0.50 |
Lifetime smoking index | 3.7 | 4.5(0.4) | 0.01 | 0.00 | 13.42 | 0.45 |
Short sleep | 3.3 | 3.5(0.1) | 0.01 | 0.00 | 2.53 | 0.36 |
Sleep duration | 3.4 | 4.1(0.3) | 0.01 | 0.00 | 0.30 | 0.22 |
Vigorous physical | 3.2 | 3.3(0.1) | 0.01 | 0.00 | 4.53 | 0.22 |
Restless leg syndrome | 3.3 | 3.4(0.1) | 0.01 | 0.00 | 0.88 | 0.16 |
Daytime napping | 3.2 | 3.6(0.2) | 0.01 | 0.00 | 0.00 | 0.00 |
Accelerometer | 3.2 | 3.3(0.1) | 0.01 | 0.00 | 0.00 | 0.00 |
Total | 19.5 | 26.7(1.6) | 0.0075 | 0.0072 | 83.39 | 0.81 |
Phenotypes | Expected Heritability | |||||
---|---|---|---|---|---|---|
Estimation | Simulation (s.d.) | AHPV | RHPV | |||
type 2 diabetes | 88.1 | - | 0.24 | - | - | - |
Short sleep * | 96.7 | 91.4(1.1) | 0.25 | 0.33 | 8.87 | 1.36 |
Daytime napping * | 99.7 | 92.5(1.1) | 0.25 | 0.32 | 11.64 | 1.33 |
Strenuous sports | 89.9 | 88.9(0.5) | 0.24 | 0.31 | 2.05 | 1.27 |
Coffee consumption * | 91.7 | 89.3(0.7) | 0.24 | 0.28 | 3.90 | 1.13 |
Educational attainment * | 429.3 | 245.9(8.0) | 0.26 | 0.27 | 79.48 | 1.11 |
Insomnia * | 151.2 | 118.4(3.4) | 0.25 | 0.26 | 41.73 | 1.07 |
Caffeine intake | 88.6 | 88.4(0.3) | 0.24 | 0.26 | 0.58 | 1.06 |
Sleep duration * | 107.1 | 97.9(1.8) | 0.24 | 0.25 | 17.73 | 1.02 |
Lifetime smoking index * | 118.9 | 104.1(1.8) | 0.24 | 0.24 | 25.91 | 1.01 |
Morningness * | 171.7 | 130.2(3.4) | 0.24 | 0.25 | 48.68 | 1.01 |
Moderate to vigorous physical activity * | 90.1 | 88.8(0.6) | 0.24 | 0.24 | 2.17 | 1.01 |
Alcohol consumption * | 109.7 | 99.9(1.9) | 0.24 | 0.22 | 19.70 | 0.92 |
Breakfast skipping | 89.1 | 88.8(0.4) | 0.24 | 0.16 | 1.07 | 0.65 |
Vigorous physical | 89.0 | 88.8(0.4) | 0.24 | 0.18 | 1.01 | 0.74 |
Restless leg syndrome | 90.4 | 92.7(0.9) | 0.24 | 0.12 | 2.59 | 0.48 |
Accelerometer | 88.1 | 88.3(0.3) | 0.24 | 0.00 | 0.00 | 0.00 |
Total | 671.3 | 324.4(9.0) | 0.2575 | 0.2599 | 86.88 | 1.07 |
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Ma, Y.; Zhou, Z.; Li, X.; Yan, Z.; Ding, K.; Chen, D. Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus. Int. J. Mol. Sci. 2021, 22, 12318. https://doi.org/10.3390/ijms222212318
Ma Y, Zhou Z, Li X, Yan Z, Ding K, Chen D. Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus. International Journal of Molecular Sciences. 2021; 22(22):12318. https://doi.org/10.3390/ijms222212318
Chicago/Turabian StyleMa, Yujia, Zechen Zhou, Xiaoyi Li, Zeyu Yan, Kexin Ding, and Dafang Chen. 2021. "Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus" International Journal of Molecular Sciences 22, no. 22: 12318. https://doi.org/10.3390/ijms222212318