The genetic risk of gestational diabetes in South Asian women
- Department of Medicine, McMaster University, Canada
- Population Health Research Institute, Canada
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Canada
- Bradford Institute for Health Research, Bradford Royal Infirmary, United Kingdom
- Department of Pathology and Molecular Medicine, McMaster University, Canada
- Population Health Science, Bristol Medical School, University of Bristol, United Kingdom
- MRC Integrative Epidemiology Unit, University of Bristol, United Kingdom
- Bristol NIHR Biomedical Research Centre, United Kingdom
Figures
Figure 1
Predicted probability of GDMIADPSG as a function of PRS (continuous), stratified by BMI groups in BiB.
Lines (with 95% confidence limits) represent predicted probabilities of GDM stratified by BMI groups (upper, middle, and lower terciles). Models are adjusted for maternal age. BiB, Born in Bradford; …
Figure 2
Multivariable regression of PRS (continuous) fasting plasma glucose (FPG) stratified by diet quality score in START.
Regression lines (with 95% confidence limits) represent predictions of FPG. Models are adjusted for maternal age, and BMI. BMI, body mass index; PRS, polygenic risk score; START, SouTh Asian BiRth …
Tables
Table 1
Characteristics of START and BiB study participants included in the analysis.
| START | BiB | |||||
|---|---|---|---|---|---|---|
| No GDM | GDM | p Value | No GDM | GDM | p Value | |
| N (%) | 759 (75) | 253 (25) | – | 3809 (88.8) | 481 (11.2) | – |
| Age, years | 29.8 (3.8) | 31.6 (4) | 5.55×10–10 | 27.7 (5) | 30.5 (5.4) | 1.40×10–22 |
| Height, cm | 162.5 (6.27) | 161.13 (6.01) | 0.002 | 159.9 (5.69) | 158.3 (5.66) | 6.19×10–08 |
| Weight, kg a | 61.7 (11.7) | 65.6 (12.9) | 2.00×10–05 | 64.8 (14.1) | 71.1 (15.1) | 2.22×10–16 |
| BMI, kg/m2 b | 23.4 (4.3) | 25.3 (4.9) | 4.93×10–08 | 25.4 (5.2) | 28.4 (5.8) | 5.89×10–23 |
| Parity, n (%) | ||||||
| 0 | 328 (44.3%) | 78 (31.1%) | 0.001 | 1189 (32.2%) | 129 (27.4%) | 5.03×10–07 |
| 1 | 299 (40.4%) | 122 (48.6%) | 1026 (27.8%) | 94 (20%) | ||
| 2 or more | 114 (15.4%) | 51 (20.3%) | 1473 (39.9%) | 248 (52.7%) | ||
| Post-secondary education, n (%) | 641 (84.6%) | 208 (82.2%) | 0.43 | 952 (29.4%) | 110 (26.3%) | 0.22 |
| Country of origin/ancestry, n (%) | ||||||
| India | 567 (74.7%) | 160 (63.2%) | 0.001 | 175 (5.2%) | 19 (4.3%) | 0.37 c |
| Pakistan | 163 (21.5%) | 74 (29.2%) | 3198 (94.2%) | 425 (95.5%) | ||
| Other | 29 (3.8%) | 19 (7.5%) | 23 (0.7%) | 1 (0.2%) | ||
| Born in South Asia, n (%) | 671 (88.5%) | 225 (88.9%) | 0.95 | 1836 (54.2%) | 291 (65.7%) | 6.50×10–06 |
| Years in recruitment country (Canada/UK) d | 6.4 (5.8) | 7.4 (5.8) | 0.02 | 9.3 (9) | 12.1 (9.4) | 3.88×10–06 |
| Parental history of diabetes, n (%) | 282 (37.3%) | 142 (56.1%) | 2.25×10–07 | 891 (27.4%) | 170 (38.9%) | 8.88×10–07 |
| Vegetarians, n (%) | 266 (37%) | 84 (34.6%) | 0.54 | 12 (1.3%) | 1 (1.1%) | >0.99 c |
| Low diet quality, n (%) | 180 (24) | 88 (35.1) | 8.00×10–04 | – | – | – |
| Polygenic risk score (z-scores) | –0.11 (1) | 0.347 (0.93) | 1.51×10–08 | –0.04 (0.99) | 0.32 (1.04) | 4.98×10–12 |
| Polygenic risk score | ||||||
| Tertile 1 | 240 (37.7%) | 39 (19.4%) | 2.74×10–06 | 1309 (34.4%) | 117 (24.3%) | 7.60×10–10 |
| Tertile 2 | 206 (32.4%) | 73 (36.3%) | 1291 (33.9%) | 142 (29.5%) | ||
| Tertile 3 | 190 (29.9%) | 89 (44.3%) | 1209 (31.7%) | 222 (46.2%) | ||
| Fasting plasma glucose, mmol/L | 4.27 (0.32) | 5.02 (0.83) | 5.51×10–32 | 4.53 (0.41) | 5.34 (1.14) | 3.18×10–43 |
| 1 hr post-load glucose, mmol/L | 7.31 (1.38) | 10.26 (2.02) | 6.04×10–57 | – | – | – |
| 2 hr post-load glucose, mmol/L | 5.96 (1.16) | 8.47 (2.16) | 1.53×10–42 | 5.49 (1.02) | 9.14 (1.97) | 1.57×10–155 |
| Area under curve glucose, mmol.hr e | 12.43 (1.83) | 17.02 (2.89) | 2.27×10–63 | 10.02 (1.21) | 14.48 (2.77) | 3.82×10–133 |
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Characteristics of participants with available PRS and GDM IADPSG, FPG, 1 hr, 2 hr post-load glucose levels or AUC glucose data. Presented data are means (standard deviation) unless otherwise indicated. p Values are calculated from Chi-squared test for categorical variables and independent t-test for continuous variables. a Pre-pregnancy values in START vs. weight at antenatal clinic (average 12 completed weeks of pregnancy) in BiB. b Derived using height measured at initial visit (in both studies) and pre-pregnancy weights (START) or antenatal clinic weights (BiB).c Approximation may be incorrect due to small counts. d Canada for START samples and UK for BiB. e Derived using fasting, 1 hr and 2 hr post-load measurements in START vs. fasting and 2 hr post-load measurements in BiB. Abbreviations: AUC, area under the curve glucose; BiB, Born in Bradford; BMI, body mass index; GDM, gestational diabetes mellitus; IADPSG, International Association of Diabetes and Pregnancy Study Groups; START, south Asian birth cohort; T2D, type 2 diabetes; UK, United Kingdom; vs., versus.
Table 2
Association between GDM risk factors and GDM-related traits: results from multivariate models in START and BiB cohorts.
| Dependent variable | Independent variables | START | BiB | Meta-analysis | |||||
|---|---|---|---|---|---|---|---|---|---|
| Beta/OR [95% CI] | p Value | Beta/OR [95% CI] | p Value | Beta (SE)/OR [95% CI] | p Value | I2 | QE p value | ||
| Fasting glucose | PRS (per 1 SD increase) | 0.083 [0.043–0.123] | 6.00×10–05 | 0.085 [0.065–0.105] | 1.67×10–16 | 0.085 [0.067–0.103] | 2.85×10–20 | 0 | 0.92 |
| Age (year) | 0.021 [0.01–0.032] | 2.00×10–04 | 0.014 [0.009–0.019] | 2.49×10–08 | 0.015 [0.011–0.02] | 4.19×10–11 | 22 | 0.26 | |
| BMI (kg/m2) | 0.024 [0.014–0.033] | 5.51×10–07 | 0.032 [0.028–0.036] | 6.53×10–53 | 0.031 [0.027–0.034] | 7.99×10–60 | 63 | 0.1 | |
| Born in South Asia (Yes/No) | 0.037 [−0.088 to 0.162] | 0.56 | 0.08 [0.039–0.122] | 2.00×10–04 | 0.076 [0.037–0.115] | 2.00×10–04 | 0 | 0.52 | |
| Parental history of T2D (Yes/No) | 0.04 [−0.043 to 0.123] | 0.34 | 0.066 [0.02–0.111] | 0.005 | 0.06 [0.02–0.1] | 0.003 | 0 | 0.6 | |
| Parity | –0.046 [−0.102 to 0.01] | 0.11 | –0.015 [−0.033 to 0.004] | 0.13 | –0.018 [−0.036 to 0] | 0.05 | 9 | 0.29 | |
| Education level (per level) | –0.031 [−0.068 to 0.006] | 0.1 | –0.016 [−0.035 to 0.002] | 0.09 | –0.019 [−0.036 to −0.002] | 0.02 | 0 | 0.49 | |
| Low diet quality (Yes/No) | 0.102 [0.01–0.193] | 0.03 | – | – | – | – | – | – | |
| 2 hr postload glucose | PRS (per 1 SD increase) | 0.189 [0.068–0.311] | 0.002 | 0.211 [0.156–0.266] | 7.87×10–14 | 0.207 [0.157–0.257] | 5.49×10–16 | 0 | 0.75 |
| Age (year) | 0.127 [0.093–0.161] | 8.34×10–13 | 0.068 [0.055–0.082] | 8.82×10–23 | 0.076 [0.064–0.089] | 1.49×10–32 | 90 | 0.002 | |
| BMI (kg/m2) | 0.047 [0.019–0.074] | 0.001 | 0.064 [0.053–0.075] | 1.43×10–29 | 0.062 [0.051–0.072] | 3.44×10–32 | 23 | 0.25 | |
| Born in South Asia (Yes/No) | 0.298 [−0.08 to 0.675] | 0.12 | 0.308 [0.195–0.422] | 1.14×10–07 | 0.308 [0.199–0.416] | 3.09×10–08 | 0 | 0.96 | |
| Parental history of T2D (Yes/No) | 0.361 [0.109–0.613] | 0.005 | 0.242 [0.117–0.366] | 1.00×10–04 | 0.265 [0.154–0.377] | 3.23×10–06 | 0 | 0.4 | |
| Parity | –0.279 [−0.45 to −0.109] | 0.001 | –0.095 [−0.146 to −0.043] | 3.00×10–04 | –0.11 [−0.16 to −0.061] | 1.00×10–05 | 76 | 0.04 | |
| Education level (per level) | –0.063 [−0.176 to 0.051] | 0.28 | –0.073 [−0.124 to −0.022] | 0.005 | –0.071 [−0.118 to −0.025] | 0.002 | 0 | 0.87 | |
| Low diet quality (Yes/No) | 0.365 [0.086–0.644] | 0.01 | – | – | – | – | – | – | |
| AUC glucose | PRS (per 1 SD increase) | 0.165 [0.099–0.231] | 1.08×10–06 | 0.152 [0.119–0.185] | 2.50×10–19 | 0.155 [0.125–0.184] | 7.74×10–25 | 0 | 0.74 |
| Age (per year) | 0.068 [0.05–0.087] | 1.16×10–12 | 0.043 [0.035–0.051] | 1.01×10–24 | 0.047 [0.039–0.054] | 3.34×10–35 | 84 | 0.01 | |
| BMI (kg/m2) | 0.047 [0.032–0.062] | 2.12×10–09 | 0.047 [0.041–0.054] | 8.89×10–44 | 0.047 [0.041–0.053] | 4.27×10–53 | 0 | 0.94 | |
| Born in South Asia (Yes/No) | 0.081 [−0.123 to 0.285] | 0.44 | 0.201 [0.133–0.269] | 8.15×10–09 | 0.189 [0.124–0.253] | 1.01×10–08 | 17 | 0.27 | |
| Parental history of T2D (Yes/No) | 0.122 [−0.015 to 0.258] | 0.08 | 0.138 [0.063–0.213] | 3.00×10–04 | 0.134 [0.069–0.2] | 6.00×10–05 | 0 | 0.83 | |
| Parity | –0.122 [−0.214 to −0.029] | 0.01 | –0.057 [−0.088 to −0.026] | 3.00×10–04 | –0.063 [−0.093 to −0.034] | 2.00×10–05 | 41 | 0.19 | |
| Education level (per level) | –0.045 [−0.106 to 0.016] | 0.15 | –0.045 [−0.075 to −0.014] | 0.004 | –0.045 [−0.072 to −0.017] | 0.001 | 0 | 0.99 | |
| Low diet quality (Yes/No) | 0.215 [0.064–0.366] | 0.005 | – | – | – | – | – | – | |
| GDM (IADPSG criteria) | PRS (per 1 SD increase) | 1.56 [1.3–1.88] | 2.97×10–06 | 1.42 [1.27–1.59] | 1.09×10–09 | 1.45 [1.32–1.6] | 2.27×10–14 | 0 | 0.4 |
| Age (year) | 1.13 [1.07–1.19] | 2.50×10–06 | 1.1 [1.07–1.13] | 1.07×10–13 | 1.11 [1.08–1.13] | 1.98×10–18 | 0 | 0.4 | |
| BMI (kg/m2) | 1.08 [1.04–1.12] | 1.00×10–04 | 1.08 [1.06–1.11] | 1.01×10–14 | 1.08 [1.06–1.1] | 6.25×10–18 | 0 | 0.87 | |
| Born in South Asia (Yes/No) | 1.35 [0.78–2.43] | 0.3 | 1.72 [1.35–2.19] | 1.00×10–05 | 1.65 [1.33–2.06] | 8.37×10–06 | 0 | 0.44 | |
| Parental history of T2D (Yes/No) | 1.67 [1.17–2.38] | 0.005 | 1.53 [1.21–1.94] | 5.00×10–04 | 1.57 [1.29–1.92] | 7.06×10–06 | 0 | 0.69 | |
| Parity | 0.86 [0.68–1.09] | 0.23 | 0.87 [0.79–0.95] | 0.003 | 0.87 [0.79–0.95] | 0.001 | 0 | 0.99 | |
| Education level (per level) | 0.89 [0.76–1.05] | 0.18 | 0.9 [0.81–0.99] | 0.04 | 0.9 [0.82–0.98] | 0.01 | 0 | 0.96 | |
| Low diet quality (Yes/No) | 1.68 [1.14–2.47] | 0.008 | – | – | – | – | – | – | |
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Models were additionally adjusted for the first five principal components (PCs) of each study. Abbreviations: BiB, Born in Bradford; BMI, Body mass index; CI, Confidence interval; GDM, Gestational diabetes mellitus; IADPSG, International Association of Diabetes and Pregnancy Study Groups; OR, Odds ratio; QE P, P-value from the test for (residual) heterogeneity; SA, South Asia; SD, Standard deviation; START, South Asian birth cohort; T2D, Type 2 diabetes.
Table 3
Population attributable fractions of GDM risk factors in mothers from the START and Born in Bradford studies (multivariable models).
| Independent variable | START | BiB | Meta-analysis | |||||
|---|---|---|---|---|---|---|---|---|
| AF [95% CI] | p Value | AF [95% CI] | p Value | AF [95% CI] | p Value | I2 | QE p value | |
| Age (29–31 vs. <29 years) | 5.6 [−9.1 to 20.2] | 0.46 | 8.3 [3.5–13] | 6.00×10–04 | 8 [3.5–12.5] | 5.00×10–04 | 0 | 0.73 |
| Age (>32 vs. <29 years) | 31.2 [17.1–45.3] | 1.00×10–05 | 20.2 [14.8–25.7] | 4.72×10–13 | 21.7 [16.6–26.8] | 9.19×10–17 | 50 | 0.16 |
| Body mass index (≥23 vs.<23) | 21.8 [8.7–34.9] | 0.001 | 33.8 [25.4–42.2] | 2.47×10–15 | 30.3 [23.3–37.4] | 3.59×10–17 | 56 | 0.13 |
| Born in SA (Yes vs. No) | 13.5 [−17.2 to 44.3] | 0.39 | 19.3 [12.6–26] | 1.47×10–08 | 19 [12.5–25.6] | 1.07×10–08 | 0 | 0.72 |
| Education (Post-secondary vs. less) | –18.2 [−46.8 to 10.5] | 0.21 | –0.8 [−4.6 to 3.1] | 0.7 | –1.1 [−4.9 to 2.7] | 0.58 | 28 | 0.24 |
| Parental history of T2D (Yes vs. No) | 15.1 [4.4–25.7] | 0.005 | 8.3 [4.1–12.5] | 1.00×10–04 | 9.2 [5.3–13.1] | 3.54×10–06 | 26 | 0.24 |
| PRS (Tertile 3 vs. 1+2) | 13.8 [4.9–22.6] | 0.002 | 12.2 [7.8–16.6] | 5.14×10–08 | 12.5 [8.6–16.5] | 4.47×10–10 | 0 | 0.76 |
| Low Diet Quality (Yes vs. No) | 8.9 [1.5–16.4] | 0.02 | – | – | – | – | – | – |
| Sum PAF of PRS (T3) and parental history of diabetes | 28.9 | 20.5 | 21.7 | |||||
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GDM status derived using IADPSG criteria. Multivariate models included age, BMI, region of birth (South Asia vs other), education, parental history of diabetes, parity, principal components 1–5, and diet quality (START only) when applicable. Abbreviations: BiB, Born in Bradford; BMI, Body mass index, CI, Confidence interval; GDM, Gestational diabetes mellitus; IADPSG, International Association of Diabetes and Pregnancy Study Groups; PAF, Population attributable fraction; PRS, Polygenic risk score; QE P, P-value from the test for (residual) heterogeneity; START, SouTh Asian BiRth CohorT.
Table 4
Interaction effects between GDM risk factors and T2D PRS in START and BiB.
| Interaction term | Dependent variable | START | BiB | Meta-analysis | |||||
|---|---|---|---|---|---|---|---|---|---|
| Beta/OR [95% CI]a | Pinteraction | Beta/OR [95% CI]a | Pinteraction | QE p value | I2 | Beta/OR [95% CI] a | Pinteraction | ||
| Fasting glucose | PRS×Age | –0.006 [−0.016 to 0.003] | 0.2 | 0.004 [0–0.008] | 0.07 | 0.002 [−0.001 to 0.006] | 0.23 | 72 | 0.06 |
| PRS×BMI | –0.01 [−0.019 to −0.002] | 0.01 | 0.004 [0–0.008] | 0.05 | 0.001 [−0.002 to 0.005] | 0.42 | 89 | 0.002 | |
| PRS×Born in South Asia | –0.137 [−0.268 to −0.006] | 0.04 | 0.037 [−0.003 to 0.078] | 0.07 | 0.022 [−0.016 to 0.061] | 0.26 | 84 | 0.01 | |
| PRS×Parental history of T2D | –0.059 [−0.139 to 0.022] | 0.15 | 0.016 [−0.028 to 0.061] | 0.48 | –0.001 [−0.04 to 0.037] | 0.94 | 61 | 0.11 | |
| PRS×Parity | –0.014 [−0.062 to 0.034] | 0.56 | 0.004 [−0.01 to 0.018] | 0.6 | 0.002 [−0.011 to 0.016] | 0.73 | 0 | 0.48 | |
| PRS×Education level | –0.014 [−0.05 to 0.022] | 0.45 | –0.005 [−0.022 to 0.013] | 0.6 | –0.006 [−0.022 to 0.009] | 0.42 | 0 | 0.65 | |
| PRS×Low diet quality | 0.141 [0.053–0.228] | 0.002 | – | – | – | – | – | – | |
| 2 hr post-load glucose | PRS×Age | 0 [−0.03 to 0.03] | 0.98 | 0.01 [−0.001 to 0.021] | 0.07 | 0.009 [−0.001 to 0.019] | 0.08 | 0 | 0.54 |
| PRS×BMI | –0.022 [−0.047 to 0.003] | 0.09 | 0 [−0.01 to 0.011] | 0.94 | –0.003 [−0.012 to 0.007] | 0.56 | 61 | 0.11 | |
| PRS×Born in South Asia | –0.191 [−0.586 to 0.205] | 0.34 | 0.072 [−0.039 to 0.182] | 0.2 | 0.053 [−0.054 to 0.159] | 0.33 | 36 | 0.21 | |
| PRS×Parental history of T2D | –0.092 [−0.335 to 0.151] | 0.46 | 0.055 [−0.066 to 0.177] | 0.37 | 0.026 [−0.083 to 0.135] | 0.64 | 11 | 0.29 | |
| PRS×Parity | –0.039 [−0.184 to 0.107] | 0.6 | 0.009 [−0.03 to 0.047] | 0.66 | 0.005 [−0.032 to 0.043] | 0.77 | 0 | 0.54 | |
| PRS×Education level | 0.037 [−0.072 to 0.146] | 0.51 | 0.008 [−0.039 to 0.056] | 0.73 | 0.013 [−0.031 to 0.056] | 0.56 | 0 | 0.64 | |
| PRS×Low diet quality | 0.068 [−0.199 to 0.335] | 0.62 | – | – | – | – | – | – | |
| AUC glucose | PRS×Age | –0.007 [−0.023 to 0.009] | 0.41 | 0.004 [−0.002 to 0.011] | 0.19 | 0.003 [−0.003 to 0.009] | 0.36 | 37 | 0.21 |
| PRS×BMI | –0.014 [−0.027 to 0] | 0.05 | 0.002 [−0.004 to 0.008] | 0.52 | –0.001 [−0.006 to 0.005] | 0.82 | 77 | 0.04 | |
| PRS×Born in South Asia | –0.126 [−0.34 to 0.088] | 0.25 | 0.015 [−0.051 to 0.081] | 0.65 | 0.003 [−0.06 to 0.066] | 0.93 | 35 | 0.22 | |
| PRS×Parental history of T2D | –0.027 [−0.158 to 0.105] | 0.69 | 0.025 [−0.048 to 0.098] | 0.49 | 0.013 [−0.051 to 0.077] | 0.68 | 0 | 0.5 | |
| PRS×Parity | –0.057 [−0.135 to 0.022] | 0.16 | 0.006 [−0.017 to 0.029] | 0.6 | 0.001 [−0.021 to 0.023] | 0.91 | 56 | 0.13 | |
| PRS×Education level | 0.007 [−0.052 to 0.066] | 0.82 | –0.008 [−0.036 to 0.021] | 0.6 | –0.005 [−0.03 to 0.021] | 0.71 | 0 | 0.67 | |
| PRS×Low diet quality | 0.07 [−0.074 to 0.214] | 0.34 | – | – | – | – | – | – | |
| GDM (IADPSG criteria) | PRS×Age | 0.99 [0.94–1.03] | 0.59 | 0.99 [0.96–1.01] | 0.17 | 0.99 [0.97–1] | 0.14 | 0 | 0.92 |
| PRS×BMI | 0.97 [0.94–1.01] | 0.15 | 0.98 [0.96–1] | 0.03 | 0.98 [0.96–0.99] | 0.01 | 0 | 0.76 | |
| PRS×Born in South Asia | 0.65 [0.33–1.23] | 0.2 | 1.04 [0.82–1.31] | 0.76 | 0.98 [0.79–1.23] | 0.89 | 41 | 0.19 | |
| PRS×Parental history of T2D | 0.72 [0.5–1.04] | 0.08 | 1.07 [0.85–1.35] | 0.59 | 0.95 [0.78–1.16] | 0.63 | 67 | 0.08 | |
| PRS×Parity | 0.88 [0.71–1.09] | 0.23 | 0.99 [0.92–1.07] | 0.86 | 0.98 [0.91–1.05] | 0.57 | 15 | 0.28 | |
| PRS×Education level | 1.01 [0.85–1.19] | 0.93 | 0.93 [0.85–1.02] | 0.12 | 0.95 [0.87–1.03] | 0.2 | 0 | 0.4 | |
| PRS×Low diet quality | 1.26 [0.85–1.89] | 0.26 | – | – | – | – | – | – | |
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Nominally significant results are shown in bold. Results from models adjusted for age, BMI, education level, birth region (South Asia vs. other), parity, parental history of diabetes, and genetic PC axes 1–5. a Values are Beta for continuous dependent variables (fasting 2 hr, and AUC glucose), and OR for binary variable (i.e. GDM). Abbreviations: AUC, area under the curve; BiB, Born in Bradford; BMI, body mass index; CI, confidence interval; GDM, gestational diabetes mellitus; IADPSG, International Association of Diabetes and Pregnancy Study Groups; OR, odds ratio; PRS, polygenic risk score; QE P, P-value from the test for (residual) heterogeneity; START, SouTh Asian BiRth CohorT.
Additional files
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Supplementary file 1
Supplementary tables.
(a) Information on the variants included in the polygenic risk score. Genomic positions corresponds to GRCh37/hg19 assembly. SNV IDs, alleles, ORs and P-values are from Mahajan et al., 2014 (Main text reference 30). Abbreviations: CI, confidence interval; OR, odds ratio; PRS, polygenic risk score. (b) Association results between PRS and GDM-related variables in START and BiB (Univariate models). a Values are Betas for continuous variables (fasting 2 h, and AUC glucose), and ORs for binary variable (i.e. GDM). Abbreviations: BiB, Born in Bradford; CI, confidence interval; IADPSG, International association of the diabetes and pregnancy study groups; OR, odds ratio; PRS, polygenic risk score; QE P, P-value from the test for (residual) heterogeneity; SE, standard error; START, South Asian birth cohort; T1, tertile 1; T2, tertile 2; T3, tertile3. (c) Association between GDM risk factors and GDM (South Asian-specific definition): results from multivariate models in START and BiB cohorts. Models were additionally adjusted for the first 5 PCs of each study. a Values are Betas for continuous variables (fasting 2 h, and AUC glucose), and ORs for binary variable (i.e. GDM). Abbreviations: BiB, Born in Bradford; BMI, Body mass index; CI, Confidence interval; GDM, Gestational diabetes mellitus; OR, Odds ratio; SA, South Asia; SD, Standard deviation; QE P, P-value from the test for (residual) heterogeneity; START, South Asian birth cohort; T2D, Type 2 diabetes. (d) Association between categorical PRS (tertiles) and GDM-related traits in multivariate models. The table shows results for tertile 2 vs. tertile 1, and tertile 3 vs. tertile 1 a Values are Betas for continuous variables (fasting 2 h, and AUC glucose), and ORs for binary variables (i.e. GDM). Abbreviations: BiB, Born in Bradford; CI, confidence interval; IADPSG, International association of the diabetes and pregnancy study groups; OR, odds ratio; PRS, polygenic risk score; QE P, P-value from the test for (residual) heterogeneity; SE, standard error; START, South Asian birth cohort; T1, tertile 1; T2, tertile 2; T3, tertile3. (e) Interaction effects between GDM risk factors and T2D PRS on GDM (South Asian-specific definition) in START and BiB. Results from models adjusted for age, BMI, education level, birth region (South Asia vs. other), parity, parental history of diabetes, and genetic PC axes 1–5. a Values are Beta for continuous dependent variables (fasting 2 h, and AUC glucose), and OR for binary variable (i.e. GDM). Abbreviations: AUC, area under the curve; BiB, Born in Bradford; BMI, body mass index; CI, confidence interval; GDM, gestational diabetes mellitus; OR, odds ratio; PRS, polygenic risk score; QE P, P-value from the test for (residual) heterogeneity; START, South Asian birth cohort. (f) Association of PRS with fasting glucose levels and GDM by BMI, birth country (South Asia vs. others), and diet quality categories in START and BiB. Results from models adjusted for age, education level, parity, and genetic PC axes 1–5, birth region (South Asia vs. other) (rows 1–3), and BMI (rows 4–7). a Values are Beta for continuous dependent variables (i.e. fasting glucose), and OR for binary variables (i.e. GDM). Abbreviations: BiB, Born in Bradford; BMI, body mass index; CI, confidence interval; GDM, gestational diabetes mellitus; IADPSG, International association of the diabetes and pregnancy study groups; PRS, polygenic risk score; SE, Standard error; START, South Asian birth cohort.
- https://cdn.elifesciences.org/articles/81498/elife-81498-supp1-v2.xlsx
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MDAR checklist
- https://cdn.elifesciences.org/articles/81498/elife-81498-mdarchecklist1-v2.pdf
