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Supplementary Online Content Mok PLH, Pedersen CB, Springate D, et al. Parental psychiatric disease and risks of attempted suicide and violent criminal offending in offspring: a population-based cohort study. JAMA Psychiatry. Published online August 31, 2016. doi:10.1001/jamapsychiatry.2016.1728 etable 1. Diagnostic classification of mental disorders according to the ICD-10-DCR and equivalent ICD-8 etable 2. Incidence rate ratios (and 95% CIs) for offspring suicide attempt and violent offending in relation to at least one parent affected by a specific psychiatric diagnosis, with additional adjustment for parental SES eresults 1. Interactions between parental socio-economic status and parental mental disorder etable 3. Incidence rate ratios of suicide attempt and violent offending in relation to having at least one parent affected by a mental disorder, stratified by parental SES eresults 2. Risks of offspring suicide attempt and violent offending by gender of affected parent and gender of offspring etable 4. Incidence rate ratios (and 95% CIs) for suicide attempt stratified by offspring gender in relation to having at least one parent affected by a specific psychiatric diagnosis or a history of suicide attempt etable 5. Incidence rate ratios (and 95% CI) for violent offending stratified by offspring gender in relation to having at least one parent affected by a specific psychiatric diagnosis or a history of suicide attempt ereferences This supplementary material has been provided by the authors to give readers additional information about their work.

etable 1. Diagnostic classification of mental disorders according to the ICD-10-DCR and equivalent ICD-8 a Diagnosis ICD-10-DCR Equivalent ICD-8 codes codes b Any mental disorders F00-F99 290-315 Organic mental disorders F00-F09 290.09, 290.10, 290.11, 290.18, 290.19, 292.x9, 293.x9, 294.x9, 309.x9 Dementia in Alzheimer F00 290.09, 290.10, 290.19 disease Vascular dementia F01 293.09, 293.19 Any substance use disorders F10-F19 291.x9, 294.39, 303.x9, 303.20, 303.28, 303.90, 304.x9 Alcohol misuse F10 291.x9, 303.x9, 303.20, 303.28, 303.90 Cannabis misuse F12 304.59 Broadly-defined schizophrenia F20-F29 295.x9, 296.89, 297.x9, 298.29-298.99, 299.04, 299.05, 299.09, 301.83 Narrowly-defined F20 295.x9 (excluding 295.79) schizophrenia Schizoaffective disorder F25 295.79, 296.89 Mood disorders F30-F39 296.x9 (excluding 296.89), 298.09, 298.19, 300.49, 301.19 Bipolar disorder F30-F31 296.19, 296.39, 298.19 Recurrent depressive F33 296.09, 296.29, 298.09, 300.49 c disorder Single and recurrent F32-F33 296.09, 296.29, 298.09, 300.49 depressive disorders Anxiety and somatoform disorders F40-F48 300.x9 (excluding 300.49), 305.x9, 305.68, 307.99 Obsessive-compulsive disorder F42 300.39

Specific personality disorders F60 301.x9 (excluding 301.19), 301.80, 301.81, 301.82, 301.84 Antisocial personality F60.2 301.79, 301.82 disorder Borderline-type personality disorder F60.31 301.84 a Between 1969 and 1993 the diagnostic system used was the Danish modification of the International Classification of Diseases, 8th revision (ICD-8) 1 and, from 1994, the International Classification of Diseases, 10th revision, Diagnostic Criteria for Research (ICD-10-DCR). 2 b Inclusive of diagnostic categories for which a valid conversion to the ICD-8 code was possible. c For recurrent depressive disorder, onset was defined as the second admission that occurred at least 8 weeks after last discharge with these ICD-8 codes.

etable 2. Incidence rate ratios (and 95% CIs) for offspring suicide attempt and violent offending in relation to at least one parent affected by a specific psychiatric diagnosis, with additional adjustment for parental SES a,b Parental psychiatric diagnosis or suicide Offspring suicide Offspring violent attempt attempt offending Any mental disorders 1.85 (1.81-1.90) 1.56 (1.53-1.59) Organic mental disorders 1.44 (1.34-1.54) 1.18 (1.10-1.26) Dementia in Alzheimer disease 1.29 (1.05-1.57) 0.81 (0.63-1.01) Vascular dementia 0.99 (0.72-1.32) 1.11 (0.83-1.45) Any substance use disorders 1.91 (1.85-1.97) 1.75 (1.71-1.80) Alcohol misuse 1.86 (1.81-1.92) 1.69 (1.64-1.74) Cannabis misuse 1.77 (1.61-1.95) 1.90 (1.74-2.06) Broadly-defined schizophrenia 1.37 (1.30-1.44) 1.19 (1.13-1.25) Narrowly-defined schizophrenia 1.32 (1.21-1.43) 1.11 (1.02-1.20) Schizoaffective disorder 1.35 (1.16-1.55) 1.01 (0.86-1.17) Mood disorders 1.58 (1.53-1.63) 1.25 (1.21-1.29) Bipolar disorder 1.25 (1.15-1.36) 1.09 (1.00-1.19) Recurrent depressive disorder 1.48 (1.40-1.57) 1.19 (1.12-1.26) Single and recurrent depressive 1.56 (1.50-1.61) 1.24 (1.20-1.29) di Anxiety d and somatoform disorders 1.88 (1.83-1.93) 1.60 (1.55-1.64) Obsessive-compulsive disorder 1.39 (1.13-1.69) 0.97 (0.76-1.20) Specific personality disorders 1.75 (1.70-1.81) 1.48 (1.44-1.53) Borderline type personality disorder 1.74 (1.57-1.92) 1.44 (1.30-1.60) Antisocial personality disorder 2.06 (1.94-2.20) 1.76 (1.66-1.87) Attempted suicide 2.10 (2.02-2.19) 1.92 (1.85-1.99) a IRRs adjusted for offspring sex and age, calendar year, and the interactions between these variables, and additionally for parental SES [maternal and paternal income (annual quintiles), highest level of education (primary school, high school/vocational training, higher education), and employment status (employed, unemployed, outside workforce for other reasons)]. b Reference group: neither parent had the particular exposure of interest.

eresults 1. Interactions between parental socio-economic status and parental mental disorder We found significant interactions between any parental mental disorders and parental socio-economic status (SES) for the risk of both adverse offspring outcomes [χ 2 (22)=120.8, p<0.001 for suicide attempt; χ 2 (22)=170.4, p<0.001 for violent offending]. To examine the interaction effects further, we stratified SES as lower, middle, and higher, applying the classifications as described previously. 3 These results, in relation to having at least one parent affected by a mental disorder, are shown in etable 3. The reference group for IRR estimation within each SES stratum was the group with no parental history of mental illness. For both offspring suicide attempt and violent offending, a stronger association between parental mental illness and offspring adverse outcomes was found in the lower SES than in the higher SES stratum.

etable 3. Incidence rate ratios of suicide attempt and violent offending in relation to having at least one parent affected by a mental disorder, stratified by parental SES a Parental SES Suicide attempt Violent offending Lower 2.31 (2.23-2.39) 1.97 (1.91-2.03) Middle 2.20 (2.13-2.27) 1.87 (1.82-1.93) Higher 1.85 (1.65-2.05) 1.62 (1.43-1.82) a Adjusted for offspring sex and age, calendar year, and the interactions between these variables.

eresults 2. Risks of offspring suicide attempt and violent offending by gender of affected parent and gender of offspring The Figure in the main article shows the IRRs for offspring suicide attempt and violent offending in relation to whether the mother only, father only, or both parents had a history of any psychiatric diagnosis or suicide attempt, stratified by offspring gender. Compared with having only one affected parent, a history of psychiatric disease in both parents was associated with doubled risks of attempted suicide and violent offending in offspring. There was, however, little variability in relative risk between exposure to maternal illness only versus exposure to paternal illness only. There was also little heterogeneity in effect size estimates for attempted suicide between male and female offspring in relation to whether both parents, or the father only, were affected. However, there was evidence of a slightly higher relative risk for female versus male offspring if exposed to maternal illness only [IRRs for female offspring 2.51 (95% CI 2.42-2.61), for male offspring 2.35 (95% CI 2.25-2.44), p = 0.015]. On the contrary, associations between parental psychiatric disease and offspring violent offending were much stronger for female than for male offspring (p <0.001), particularly when both parents were affected.

etable 4. Incidence rate ratios (and 95% CIs) for suicide attempt stratified by offspring gender in relation to having at least one parent affected by a specific psychiatric diagnosis or a history of suicide attempt a Parental psychiatric diagnosis or suicide attempt Male offspring Female offspring P value for gender interaction b 0.12 0.81 0.39 0.74 0.23 0.10 0.73 0.27 0.36 0.68 <.001 0.025 Any mental disorders Organic mental disorders 2.48 (2.41-2.18 2 56) (1.97-2.57 (2.49-2.21 2 64) (2.00- Dementia in Alzheimer disease 1.64 2 40) (1.22-1.96 2 44) (1.45- Vascular dementia 1.36 2 15) (0.86-1.50 2 58) (0.94- Any substance use disorders 2.98 2 02) (2.86-2.88 2 27) (2.77- Alcohol misuse 2.92 3 10) (2.80-2.78 2 99) (2.66- Cannabis misuse 3.64 3 05) (3.15-3.52 2 90) (3.09- Broadly-defined schizophrenia 2.05 4 17) (1.91-2.17 3 98) (2.03- Narrowly-defined schizophrenia 2.45 2 20) (2.17-2.26 2 32) (2.01- Schizoaffective disorder 2.04 2 74) (1.64-2.16 2 54) (1.76- Mood disorders 1.91 2 48) (1.82-2.16 2 62) (2.07- Bipolar disorder 1.43 2 00) (1.26-1.74 2 25) (1.55- Recurrent depressive disorder 1.72 1 62) (1.58-2.04 1 94) (1.89-0.003 Single and recurrent depressive 1.87 1 87) (1.77-2.12 2 19) (2.03- <.001 di Anxiety d and somatoform disorders 2.62 1 96) (2.52-2.63 2 22) (2.53-0.92 Obsessive-compulsive disorder 1.83 2 72) (1.32-1.94 2 72) (1.47-0.77 Specific personality disorders 2.54 2 45) (2.43-2.70 2 52) (2.59-0.038 Borderline type personality 2.74 2 65) (2.34-2.96 2 82) (2.59-0.45 di Antisocial d personality disorder 3.99 3 18) (3.65-3.94 3 37) (3.61-0.85 Attempted suicide 3.50 4 35) (3.30-3.35 4 29) (3.18-0.28 a Adjusted for offspring sex and age, calendar 3 year, 71) and the interactions 3 53) between these variables. b Statistically significant at p < 0.0025 (Bonferroni-corrected 4 significance level: 0.05/20). Bold type indicates significant gender interaction at this corrected level.

etable 5. Incidence rate ratios (and 95% CI) for violent offending stratified by offspring gender in relation to having at least one parent affected by a specific psychiatric diagnosis or a history of suicide attempt a Parental psychiatric diagnosis or suicide attempt Male offspring Female offspring P value for gender interaction b Any mental disorders 2.15 (2.11-2.20) 3.25 (3.07-3.44) <.001 Organic mental disorders 1.87 (1.74-2.02) 2.20 (1.78-2.67) 0.15 Dementia in Alzheimer 1.24 (0.96-1.56) 0.67 (0.21-1.55) 0.19 divascular dementia 1.73 (1.27-2.30) 1.49 (0.53-3.21) 0.75 Any substance use disorders 2.73 (2.66-2.81) 4.13 (3.85-4.43) <.001 Alcohol misuse 2.65 (2.57-2.73) 3.79 (3.50-4.09) <.001 Cannabis misuse 3.72 (3.39-4.07) 6.49 (5.32-7.81) <.001 Broadly-defined 1.77 (1.68-1.86) 2.70 (2.37-3.05) <.001 Narrowly-defined hi h i 1.87 (1.71-2.05) 3.25 (2.64-3.95) <.001 Schizoaffective h i disorder 1.45 (1.23-1.70) 2.45 (1.62-3.51) 0.021 Mood disorders 1.60 (1.54-1.65) 2.03 (1.85-2.22) <.001 Bipolar disorder 1.33 (1.22-1.46) 1.47 (1.14-1.88) 0.46 Recurrent depressive 1.50 (1.41-1.59) 1.75 (1.48-2.04) 0.084 di Single d and recurrent 1.58 (1.52-1.64) 1.99 (1.80-2.19) <.001 danxiety iand disomatoform d 2.25 (2.19-2.31) 3.14 (2.93-3.36) <.001 diobsessive-compulsive d 1.34 (1.04-1.69) 1.18 (0.54-2.20) 0.73 di Specific d personality disorders 2.20 (2.14-2.27) 3.34 (3.09-3.61) <.001 Borderline type personality 2.26 (2.01-2.52) 3.15 (2.40-4.04) 0.026 di Antisocial d personality 3.41 (3.20-3.63) 5.55 (4.75-6.43) <.001 di Attempted d suicide 3.14 (3.01-3.26) 4.64 (4.23-5.08) <.001 a Adjusted for offspring sex and age, calendar year, and the interactions between these variables. b Statistically significant at p < 0.0025 (Bonferroni-corrected 4 significance level: 0.05/20). Bold type indicates significant gender interaction at this corrected level.

ereferences 1. World Health Organization (WHO). Classification of Diseases: Extended Danish- Latin Version of the World Health Organization International Classification of Diseases, 8th Revision, 1965. Copenhagen: Danish National Board of Health; 1971. 2. World Health Organization (WHO). The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. Geneva: World Health Organization; 1993. 3. Webb RT, Antonsen S, Mok PLH, Agerbo E, Pedersen CB. National cohort study of suicidality and violent criminality among Danish immigrants. PLoS One. 2015 Jun 29;10(6):e0131915. 4. Bland JM, Altman DG. Multiple significance tests: the Bonferroni method. BMJ. 1995;310(6973):170.