Polygenic Risk: Predicting Depression Outcomes in Clinical and Epidemiological Cohorts of Youths
Abstract
Objective:
Methods:
Results:
Conclusions:
Methods
Samples
Psychometric Measures
Clinical cohort.
The first epidemiological cohort.
The replication epidemiological cohort.
Genotyping Methods
Data Analysis
Results
Clinical Cohort | Replication Epidemiological Cohort | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Characteristic | Case Subjects (N=279) | Control Subjects (N=187) | Epidemiological Cohort (N=1,450) | Age 8 (N=184) | Age 11 (N=317) | |||||
N | % | N | % | N | % | N | % | N | % | |
Female | 190 | 68.1 | 118 | 63.1 | 914 | 63.0 | 91 | 49.2 | 148 | 46.7 |
Maternal educationa | ||||||||||
Less than secondary school | 10 | 3.6 | 2 | 1.0 | 708 | 48.8 | 67 | 36.4 | 111 | 35.0 |
Secondary school or more | 269 | 96.4 | 185 | 98.9 | 742 | 51.2 | 117 | 63.6 | 206 | 65.0 |
Paternal education | ||||||||||
Less than secondary school | 13 | 4.7 | 5 | 2.7 | 834 | 57.5 | — | — | — | — |
Secondary school or more | 266 | 95.3 | 182 | 97.3 | 616 | 42.5 | — | — | — | — |
Childhood abuse | — | — | — | — | ||||||
None | 131 | 47.0 | 118 | 63.1 | 1,049 | 72.3 | — | — | — | — |
One or more mild abuse types | 148 | 53.0 | 69 | 36.9 | 269 | 18.6 | — | — | — | — |
One or more moderate abuse types | — | — | — | — | 86 | 5.9 | — | — | — | — |
One or more severe abuse types | — | — | — | — | 46 | 3.2 | — | — | — | — |
Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | |
Age | 14.76 | 2.00 | 14.67 | 2.45 | 13.99 | 0.92 | 8.12 | 0.30 | 11.32 | 0.52 |
Depressive symptomsb | ||||||||||
Self-report | 0.19 | 0.95 | –1.11 | 0.21 | 11.53 | 7.71 | — | — | — | — |
Maternal report | — | — | — | — | — | — | 55.30 | 6.06 | 55.24 | 6.48 |
Paternal report | — | — | — | — | — | — | 53.48 | 5.28 | 53.60 | 5.74 |
Clinical Cohort
Clinical Cohort | Epidemiological Cohort | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Case-Control Status | Depression Severity | Age at Onset | Depressive Symptoms | Longitudinal Analyses | |||||||||||
p Threshold | FDR | Original p | R2 | FDR | Original p | R2 | FDR | Original p | R2 | FDR | Original p | R2 | FDR | Original p | R2 |
p<5×10−8 | 0.965 | 0.965 | 0 | 0.307 | 0.307 | 0.000 | 0.433 | 0.433 | 0 | 0.834 | 0.834 | 0 | 0.098 | 0.067 | 0.004 |
p<1×10−5 | 0.915 | 0.784 | 0.048 | 0.051 | 0.029 | 0.014 | 0.076 | 0.054 | 0.009 | 0.584 | 0.500 | 0.000 | 0.367 | 0.367 | 0.001 |
p<1×10−4 | 0.230 | 0.164 | 0.006 | 0.045 | 0.019 | 0.017 | 0.037 | 0.005 | 0.021 | 0.099 | 0.071 | 0.001 | 0.098 | 0.070 | 0.004 |
p<1×10−3 | 0.136 | 0.078 | 0.010 | 0.087 | 0.074 | 0.008 | 0.176 | 0.148 | 0.004 | 0.028 | 0.012 | 0.003 | 0.180 | 0.154 | 0.002 |
p<0.01 | 0.003 | 0.001 | 0.030 | 0.036 | 0.01 | 0.021 | 0.047 | 0.016 | 0.015 | 0.042 | 0.024 | 0.003 | 0.098 | 0.054 | 0.005 |
p<0.05 | 4.97×10−4 | 1.17×10−4 | 0.050 | 0.029 | 0.004 | 0.018 | 0.047 | 0.02 | 0.016 | 0.020 | 0.005 | 0.004 | 0.067 | 0.010 | 0.009 |
p<0.10 | 4.97×10−4 | 1.42×10−4 | 0.047 | 0.075 | 0.053 | 0.010 | 0.067 | 0.038 | 0.010 | 0.020 | 0.006 | 0.004 | 0.067 | 0.019 | 0.007 |
Cohort, Outcome, and Model | Variable | Odds Ratio, β, or Hazard Ratio | SE | 95% CI | p (false-discovery-rate-corrected) | Original p | R2 | Model Comparison (p) |
---|---|---|---|---|---|---|---|---|
Clinical cohort | ||||||||
Case-control status (odds ratio) | ||||||||
Null model | — | — | — | — | — | — | 0.030 | — |
G | PRS | 1.560 | 1.130 | 1.230, 1.980 | 0.001 | 2.48×10−4 | 0.079 | 1.637×10−4 |
G+E | PRS | 1.578 | 1.135 | 1.230, 2.024 | 0.002 | 3.39×10−4 | 0.179 | 2.807×10−11 |
Childhood abuse | 3.924 | 1.292 | 2.376, 6.472 | 8.12×10−4 | 9.020×10−8 | |||
G×E | PRS | 1.677 | 1.171 | 1.231, 2.284 | 0.003 | 0.001 | 0.181 | 0.436 |
Childhood abuse | 3.896 | 1.289 | 2.366, 6.411 | 8.12×10−4 | 8.950×10−8 | |||
PRS and childhood abuse interaction | 0.838 | 1.300 | 0.502, 1.401 | 0.501 | 0.501 | |||
Depression severity (β) | ||||||||
Null model | — | — | — | — | — | — | 0.058 | — |
G | PRS | 0.177 | 0.069 | 0.021, 0.288 | 0.010 | 0.004 | 0.077 | 0.004 |
G+E | PRS | 0.149 | 0.066 | 0.019, 0.279 | 0.043 | 0.026 | 0.135 | 1.220×10−4 |
Childhood abuse | 0.494 | 0.126 | 0.247, 0.741 | 0.002 | 6.20×10−4 | |||
G×E | PRS | 0.239 | 0.091 | 0.060, 0.417 | 0.020 | 0.009 | 0.139 | 0.153 |
Childhood abuse | 0.519 | 0.127 | 0.270, 0.768 | 0.087 | 6.250×10−5 | |||
PRS and childhood abuse interaction | –0.187 | 0.131 | –0.444, 0.069 | 0.184 | 0.153 | |||
Age at onset (β) | ||||||||
Null model | — | — | — | — | — | — | 0.443 | — |
G | PRS | –0.375 | 0.160 | –0.688, –0.062 | 0.036 | 0.020 | 0.459 | 0.024 |
G+E | PRS | –0.374 | 0.158 | –0.683, –0.065 | 0.036 | 0.019 | 0.471 | 0.040 |
Childhood abuse | –0.600 | 0.289 | –1.167, –0.034 | 0.060 | 0.040 | |||
G×E | PRS | –0.191 | 0.238 | –0.658, 0.276 | 0.450 | 0.425 | 0.471 | 0.307 |
Childhood abuse | –0.540 | 0.295 | –1.118, 0.038 | 0.089 | 0.069 | |||
PRS and childhood abuse interaction | –0.321 | 0.313 | –0.934, 0.292 | 0.345 | 0.307 | |||
Epidemiological cohort | ||||||||
Depressive symptoms (β) | ||||||||
Null model | — | — | — | — | — | — | 0.071 | — |
G | PRS | 0.557 | 0.200 | 0.167, 0.947 | 0.012 | 0.005 | 0.075 | 0.005 |
G+E | PRS | 0.439 | 0.196 | 0.055, 0.823 | 0.038 | 0.025 | 0.107 | 5.071×10−13 |
Childhood abuse | 4.935 | 0.677 | 3.609, 6.262 | 6.080×10−6 | 5.070×10−13 | |||
G×E | PRS | 0.346 | 0.206 | –0.057, 0.748 | 0.112 | 0.093 | 0.108 | 0.131 |
Childhood abuse | 4.642 | 0.704 | 3.262, 6.022 | 3.620×10−4 | 6.040×10−11 | |||
PRS and childhood abuse interaction | 1.010 | 0.669 | –0.301, 2.320 | 0.143 | 0.131 | |||
Epidemiological cohort | ||||||||
Prospective moderate to severe depressive symptoms (hazard ratio) | ||||||||
Null model | — | — | — | — | — | — | 0.035 | — |
G | PRS | 1.202 | 0.071 | 1.045, 1.383 | 0.020 | 0.010 | 0.044 | 0.010 |
G+E | PRS | 1.171 | 0.073 | 1.016, 1.350 | 0.039 | 0.029 | 0.078 | 4.302×10−7 |
Childhood abuse | 2.817 | 0.184 | 1.963, 4.043 | 6.750×10−5 | 1.940×10−8 | |||
G×E | PRS | 1.194 | 0.079 | 1.024, 1.393 | 0.038 | 0.024 | 0.079 | 0.514 |
Childhood abuse | 2.942 | 0.193 | 2.015, 4.294 | 6.750×10−5 | 2.250×10−8 | |||
PRS and childhood abuse interaction | 0.877 | 0.201 | 0.592, 1.300 | 0.513 | 0.513 |
Epidemiological Cohorts
Discussion
PRS, Major Depression, and Child and Adolescent Depression
PRS, Major Depression, and Prediction of Future Risk
Depression PRS and Child Abuse
Limitations
Conclusions
Acknowledgments
Supplementary Material
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