Research Article

Body mass index and childhood symptoms of depression, anxiety, and attention-deficit hyperactivity disorder: A within-family Mendelian randomization study

Medical Research Council Integrative Epidemiology Unit, University of Bristol, United Kingdom
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, United Kingdom
PROMENTA Research Centre, Department of Psychology, University of Oslo, Norway
Nic Waals Institute, Lovisenberg Diaconal Hospital, Norway
Department of Mental Disorders, Norwegian Institute of Public Health, Norway
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Norway
Institute of Clinical Medicine, University of Oslo, Norway
Centre for Fertility and Health, Norwegian Institute of Public Health, Norway
Center for Diabetes Research, Department of Clinical Science, University of Bergen, Norway
Department of Clinical Science, University of Bergen, Norway
Department of Medical Genetics, Haukeland University Hospital, Norway
Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Norway
Children and Youth Clinic, Haukeland University Hospital, Norway
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Norway

Dec 20, 2022

https://doi.org/10.7554/eLife.74320

Open access
Copyright information

Figures
Tables
Additional files

6 figures, 17 tables and 3 additional files

Figures

Figure 1

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Figure 2

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BMI and child’s depressive, anxiety, and ADHD symptoms, using a polygenic score for adult BMI (N=40,949 trios).

Coefficients represent standard-deviation change in outcomes per 5 kg/m² increase in BMI, shown with 95% confidence intervals.

Figure 3

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BMI and child’s depressive, anxiety, and ADHD symptoms, using a polygenic score for childhood body size (N=40,949 trios).

Coefficients represent standard-deviation change in outcomes per 5 kg/m² increase in BMI, shown with 95% confidence intervals.

Appendix 1—figure 1

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Flow chart of inclusion and exclusion of MoBa participants into the study sample.

Appendix 1—figure 2

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Associations of child’s BMI polygenic scores with ancestry.

Associations of the child’s polygenic scores for BMI and the child’s principal components of ancestry, adjusted for the child’s genotyping centre and chip.

Appendix 1—figure 3

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Associations of child’s BMI polygenic scores with ancestry, adjusted for parental polygenic scores.

Associations of the child’s polygenic scores for BMI and the child’s principal components of ancestry, adjusted for the child’s genotyping centre and chip and the parents’ polygenic scores.

Tables

Table 1

Descriptive characteristics of analytic sample (N=40,949)*.

Continuous variables		mean	SD
Maternal age at child’s birth (years)		30.2	4.4
Paternal age at birth (years)		32.6	5.1
Maternal depressive/anxiety symptoms, Hopkins Symptoms Checklist-25 (SCL-25)^†		1.2	1.9
Paternal depressive/anxiety symptoms, Hopkins Symptoms Checklist-25 (SCL-25) ^‡		1.1	2.1
Maternal ADHD symptoms: adult ADHD self-report scale ^§		6.7	3.4
Paternal ADHD symptoms: adult ADHD self-report scale ^¶		8.3	3.1
Maternal pre-pregnancy BMI (kg/m²)		24.0	4.1
Paternal BMI (kg/m²)		25.9	3.2
Child’s BMI at age 8 (kg/m²)		16.3	2.0
Child depressive symptoms age 8: Short Mood and Feelings Questionnaire (SMFQ)**		1.9	2.5
Child anxiety symptoms age 8: Screen for Child Anxiety Related Disorders (SCARED)^††		1.0	1.2
Child ADHD symptoms age 8: Parent/Teacher Rating Scale for Disruptive Behaviour Disorders (RS-DBD) ^{‡ ‡}		8.6	7.2
Child ADHD symptoms (inattention) age 8: Parent/Teacher Rating Scale for Disruptive Behaviour Disorders (RS-DBD) ^{§ §}		5.0	4.1
Child ADHD symptoms (hyperactivity) age 8: Parent/Teacher Rating Scale for Disruptive Behaviour Disorders (RS-DBD)^{§ §}		3.6	3.9
Categorical variables	Category		%
Child’s sex	Male		51.1
Child’s sex	Female		48.9
Maternal educational qualifications	9 year elementary education		2.0
	Up to 2 years further education		4.1
	Further education: vocational		12.2
	Further education: general studies, sixth form		14.9
	Higher education: college/university, up to 4 years		42.8
	Higher education: college/university, over 4 years		24.0
Paternal educational qualifications	9 year elementary education		3.4
	Up to 2 years further education		5.6
	Further education: vocational		25.1
	Further education: general studies, sixth form		12.9
	Higher education: college/university, up to 4 years		28.4
	Higher education: college/university, over 4 years		24.4
Maternal parity at child’s birth	0		46.8
	1		35.7
	2		14.0
	3+		2.7
	4+		0.7
Mother’s marital status at birth	Married/registered partner		97.4
Mother’s marital status at birth	single		2.6
Mother’s smoking status during pregnancy	never		51.0
	Stopped before week 17		42.0
	Currently, sometimes		2.4
	Currently, daily		4.5

*

The reasons for exclusions and numbers in each case are shown in Appendix 1—figure 1. Missing data in BMI, outcomes and covariates was imputed using multiple imputation by chained equations. Descriptive statistics for the unimputed data are shown in Appendix 1.
†

Based on 5 items. Possible range: 0–15.
‡

Based on 8 items. Possible range: 0–24.
§

Possible range: 0–24.
¶

Possible range: 0–24.
**

Possible range: 0-26.
††

Possible range: 0–10.
‡ ‡

Possible range: 0–54.
§ §

Possible range: 0–27.

Appendix 1—table 1

Descriptive statistics of full MoBa sample (N=113,691)*.

Continuous variables		mean	SD	N obs
Maternal age at birth		30.1	4.6	113,691
Paternal age at birth		32.7	5.5	113,172
Maternal depressive/anxiety symptoms, based on 5 items from the Hopkins Symptoms Checklist-25 (SCL-25)^†		1.3	2.0	100,570
Paternal depressive/anxiety symptoms, based on 8 items from the Hopkins Symptoms Checklist-25 (SCL-25)^‡		1.2	2.1	77,018
Maternal ADHD symptoms: adult ADHD self-report scale^§		6.6	3.5	56,255
Paternal ADHD symptoms: adult ADHD self-report scale^¶		8.2	3.2	34,425
Maternal pre-pregnancy BMI (kg/m²)		24.0	4.1	100,060
Paternal BMI (kg/m²)		25.9	3.3	79,536
Child’s BMI at age 8 (kg/m²)		16.2	2.0	36,894
Child depressive symptoms age 8: Short Mood and Feelings Questionnaire (SMFQ)**		1.9	2.4	43,065
Child anxiety symptoms age 8: Screen for Child Anxiety Related Disorders (SCARED)^††		1.0	1.2	43,298
Child ADHD symptoms age 8: Parent/Teacher Rating Scale for Disruptive Behaviour Disorders (RS-DBD)^{‡ ‡}		8.5	7.2	43,238
Child ADHD symptoms (inattention) age 8: Parent/Teacher Rating Scale for Disruptive Behaviour Disorders (RS-DBD)^{§ §}		5.0	4.1	43,194
Child ADHD symptoms (hyperactivity) age 8: Parent/Teacher Rating Scale for Disruptive Behaviour Disorders (RS-DBD)^{§ §}		3.6	3.9	43,177
Categorical variables	Category		%	N obs
Child’s sex	male		51.3	113,477
Child’s sex	female		48.7
maternal educational qualifications	9 year elementary education		2.8	101,020
	Up to 2 years further education		5.2
	Further education: vocational		12.8
	Further education: general studies, sixth form		15.7
	Higher education: college/university, up to 4 years		40.9
	Higher education: college/university, over 4 years		22.6
paternal educational qualifications	9 year elementary education		4.8	100,891
	Up to 2 years further education		6.6
	Further education: vocational		26.2
	Further education: general studies, sixth form		13.2
	Higher education: college/university, up to 4 years		26.5
	Higher education: college/university, over 4 years		22.7
maternal parity at child’s birth	0		44.0	113,691
	1		35.9
	2		15.6
	3		3.4
	4+		1.1
Mother’s marital status at birth	Married/registered partner		95.5	113,691
Mother’s marital status at birth	single		4.5
Mother’s smoked during pregnancy	never		49.9	101,373
	Stopped before week 17		41.7
	Currently, sometimes		2.8
	Currently, daily		5.6

*

All participants in the birth registry file who had not withdrawn consent.
†

Possible range: 0–15.
‡

Possible range: 0–24.
§

Possible range: 0–24.
¶

Possible range: 0–24.
**

Possible range: 0-26.
††

Possible range: 0-10.
‡ ‡

Possible range: 0–54.
§ §

Possible range: 0–27.

Appendix 1—table 2

Descriptive statistics of analytic sample (N=40,949)*, unimputed data.

Continuous variables		mean	SD	N obs
Maternal age at birth		30.2	4.4	40,949
Paternal age at birth		32.6	5.1	40,945
Maternal depressive/anxiety symptoms, based on 5 items from the Hopkins Symptoms Checklist-25 (SCL-25)†		1.2	1.9	39,647
Paternal depressive/anxiety symptoms, based on 8 items from the Hopkins Symptoms Checklist-25 (SCL-25)^‡		1.1	2.1	38,050
Maternal ADHD symptoms: adult ADHD self-report scale^§		6.5	3.4	24,192
Paternal ADHD symptoms: adult ADHD self-report scale^¶		8.2	3.1	16,348
Maternal pre-pregnancy BMI (kg/m²)		24.0	4.1	39,323
Paternal BMI (kg/m²)		25.9	3.2	39,405
Child’s BMI at age 8 (kg/m²)		16.2	2.0	16,144
Child depressive symptoms age 8: Short Mood and Feelings Questionnaire (SMFQ)**		1.8	2.4	18,747
Child anxiety symptoms age 8: Screen for Child Anxiety Related Disorders (SCARED)^††		1.0	1.2	18,834
Child ADHD symptoms age 8: Parent/Teacher Rating Scale for Disruptive Behaviour Disorders (RS-DBD)^{‡ ‡}		8.4	7.1	18,813
Child ADHD symptoms (inattention) age 8: Parent/Teacher Rating Scale for Disruptive Behaviour Disorders (RS-DBD)^{§ §}		4.9	4.0	18,794
Child ADHD symptoms (hyperactivity) age 8: Parent/Teacher Rating Scale for Disruptive Behaviour Disorders (RS-DBD)^{§ §}		3.5	3.8	18,787
Categorical variables	Category		%	N obs
Child’s sex	male		51.0	40,949
Child’s sex	female		48.9
maternal educational qualifications	9 year elementary education		2.0	39,569
	Up to 2 years further education		4.1
	Further education: vocational		12.1
	Further education: general studies, sixth form		14.9
	Higher education: college/university, up to 4 years		42.8
	Higher education: college/university, over 4 years		24.8
paternal educational qualifications	9 year elementary education		3.4	40,062
	Up to 2 years further education		5.6
	Further education: vocational		25.1
	Further education: general studies, sixth form		12.9
	Higher education: college/university, up to 4 years		28.5
	Higher education: college/university, over 4 years		24.4
maternal parity at child’s birth	0		46.8	40,949
	1		35.7
	2		14.0
	3		2.7
	4+		0.7
Mother’s marital status at birth	Married/registered partner		97.4	40,949
Mother’s marital status at birth	single		2.6
Mother’s smoked during pregnancy	never		51.1	40,118
	Stopped before week 17		42.0
	Currently, sometimes		2.4
	Currently, daily		4.5

*

The reasons for exclusions and numbers in each case are shown in Appendix 1—figure 1.
†

Possible range: 0–15.
‡

Possible range: 0–24.
§

Possible range: 0–24.
¶

Possible range: 0–24.
**

Possible range: 0-26.
††

Possible range: 0–10.
‡ ‡

Possible range: 0–54.
§ §

Possible range: 0–27.

Appendix 1—table 3

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS (N=40,949)*.

		Non-genetic estimate^†			MR estimate ^‡			Within-families MR estimate ^‡
Outcome		Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p
Depressive symptoms: standardized SMFQ^§ score	Child BMI	0.05	0.01,0.09	0.02	0.45	0.26,0.64	<0.001	0.26	–0.01,0.52	0.06
	Mother’s BMI	0.05	0.03,0.07	<0.001				0.11	0.02,0.19	0.01
	Father’s BMI	0.01	–0.02,0.03	0.67				0.02	–0.09,0.13	0.71
Anxiety symptoms: standardized SCARED^¶ score	Child BMI	–0.07	−0.11,–0.03	0.001	–0.06	–0.25,0.12	0.51	0.01	–0.25,0.26	0.96
	Mother’s BMI	0.01	–0.01,0.03	0.47				–0.03	–0.11,0.05	0.49
	Father’s BMI	–0.00	–0.02,0.02	0.89				–0.02	–0.13,0.09	0.72
ADHD symptoms: standardized RS-DBD** score, ADHD items	Child BMI	–0.07	−0.11,–0.03	0.001	0.35	0.17,0.53	<0.001	0.36	0.09,0.63	0.009
	Mother’s BMI	0.04	0.02,0.06	<0.001				0.00	–0.08,0.09	0.97
	Father’s BMI	0.02	–0.00,0.04	0.10				–0.01	–0.12,0.09	0.80
ADHD-inattention symptoms: standardized RS-DBD** score, inattention items	Child BMI	–0.06	−0.10,–0.02	0.006	0.32	0.14,0.49	<0.001	0.38	0.12,0.65	0.005
	Mother’s BMI	0.05	0.03,0.07	<0.001				0.01	–0.08,0.09	0.86
	Father’s BMI	0.02	–0.00,0.05	0.06				–0.06	–0.17,0.04	0.24
ADHD-hyperactivity symptoms: standardized RS-DBD** score, hyperactivity items	Child BMI	–0.06	−0.10,–0.02	0.002	0.31	0.13,0.49	0.001	0.27	–0.00,0.54	0.05
	Mother’s BMI	0.03	0.01,0.05	0.005				–0.00	–0.09,0.08	0.92
	Father’s BMI	0.01	–0.01,0.04	0.32				0.04	–0.07,0.15	0.47

*

Coefficients represent S.D. change in symptoms per 5 kg/m² increase in BMI.
†

Phenotypic models adjust for the child’s sex and birth year, the mother’s parity at the child’s birth, and the mother’s and father’s: educational qualifications, depressive/anxiety and ADHD symptoms, and smoking status during pregnancy. They also adjust for the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
‡

Genetic models adjust for the child’s sex and birth year and the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
§

Short Mood and Feelings Questionnaire.
¶

Screen for Child Anxiety Related Disorders.
**

Parent/Teacher Rating Scale for Disruptive Behaviour Disorders.

Appendix 1—table 4

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS (N=40,949)*.

		Non-genetic estimate†			MR estimate ‡			Within-families MR estimate ‡
Outcome		Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p
Depressive symptoms: standardized SMFQ^§ score	Child BMI	0.05	0.01,0.09	0.02	0.08	–0.07,0.22	0.29	0.02	–0.20,0.23	0.88
	Mother’s BMI	0.05	0.03,0.07	<0.001				0.02	–0.09,0.14	0.67
	Father’s BMI	0.01	–0.02,0.03	0.67				0.05	–0.10,0.19	0.51
Anxiety symptoms: standardized SCARED^¶ score	Child BMI	–0.07	−0.11,–0.03	0.001	–0.04	–0.18,0.11	0.62	0.02	–0.18,0.23	0.83
	Mother’s BMI	0.01	–0.01,0.03	0.47				–0.02	–0.12,0.09	0.78
	Father’s BMI	–0.00	–0.02,0.02	0.89				–0.06	–0.19,0.08	0.42
ADHD symptoms: standardized RS-DBD** score, ADHD items	Child BMI	–0.07	−0.11,–0.03	0.001	–0.07	–0.21,0.07	0.35	–0.03	–0.22,0.17	0.80
	Mother’s BMI	0.04	0.02,0.06	<0.001				–0.03	–0.12,0.07	0.62
	Father’s BMI	0.02	–0.00,0.04	0.10				–0.02	–0.15,0.11	0.77
ADHD-inattention symptoms: standardized RS-DBD** score, inattention items	Child BMI	–0.06	−0.10,–0.02	0.006	–0.04	–0.18,0.11	0.63	–0.05	–0.25,0.14	0.59
	Mother’s BMI	0.05	0.03,0.07	<0.001				0.03	–0.07,0.13	0.61
	Father’s BMI	0.02	–0.00,0.05	0.06				–0.01	–0.14,0.12	0.86
ADHD-hyperactivity symptoms: standardized RS-DBD** score, hyperactivity items	Child BMI	–0.06	−0.10,–0.02	0.002	–0.08	–0.22,0.05	0.24	0.01	–0.20,0.22	0.95
	Mother’s BMI	0.03	0.01,0.05	0.005				–0.07	–0.18,0.03	0.18
	Father’s BMI	0.01	–0.01,0.04	0.32				–0.02	–0.16,0.11	0.74

*

Coefficients represent S.D. change in symptoms per 5 kg/m² increase in BMI.
†

Phenotypic models adjust for the child’s sex and birth year, the mother’s parity at the child’s birth, and the mother’s and father’s: educational qualifications, depressive/anxiety and ADHD symptoms, and smoking status during pregnancy. They also adjust for the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
‡

Genetic models adjust for the child’s sex and birth year and the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
§

Short Mood and Feelings Questionnaire.
¶

Screen for Child Anxiety Related Disorders.
**

Parent/Teacher Rating Scale for Disruptive Behaviour Disorders

Appendix 1—table 5

Associations of phenotypes and polygenic scores within parental pairs*.

Phenotypes: regression of father’s BMI, depressive symptoms, and ADHD symptoms on mother’s phenotypes
	Father’s: BMI	Father’s: Depressive symptoms	Father’s: ADHD symptoms
	Beta (95% CI), p	Beta (95% CI), p	Beta (95% CI), p
Mother’s: BMI	0.23 (0.22,0.25) p<0.001	0.01 (-0.00,0.02) p=0.09	0.03 (0.02,0.05) p<0.001
Mother’s: Depressive symptoms	0.00 (-0.01,0.01), p=0.85	0.18 (0.16,0.20) p<0.001	0.10 (0.09,0.12), P<0.001
Mother’s: ADHD symptoms	0.01 (-0.02,0.01) p=0.32	0.05 (0.05,0.06) p<0.001	0.11 (0.09,0.13) p<0.001
Polygenic scores: regression of father’s PGS for BMI, depression, and ADHD: regression of father’s PGS on mother’s PGS
	Father’s: Adult BMI PGS	Father’s: Childhood body size PGS	Father’s: Depression PGS	Father’s: ADHD PGS
	Beta (95% CI), p	Beta (95% CI), p	Beta (95% CI), p	Beta (95% CI)
Mother’s: Adult BMI PGS	0.01 (0.00,0.02), p=0.02	0.01 (0.00,0.02), p=0.008	–0.00 (-0.01,0.01), p=0.62	–0.00 (-0.01,0.01), p=0.49
Mother’s: Childhood body size PGS	0.01 (-0.00,0.02), p=0.10	0.01 (-0.00,0.02), p=0.15	0.00 (-0.00,0.01), p=0.33	0.01 (0.00,0.02), p=0.03
Mother’s: Depression PGS	–0.01 (−0.02–0.00), p=0.11	–0.00 (-0.01,0.01), p=0.76	–0.00 (-0.01,0.01), p=0.44	–0.00 (-0.01,0.01), p=0.47
Mother’s: ADHD PGS	–0.00 (-0.01,0.01), p=0.58	0.01 (-0.00,0.02), p=0.24	–0.00 (-0.01,0.01), p=0.42	–0.00 (-0.01,0.01), p=0.93

*

All models adjusted for the first 20 principal components of ancestry, genotyping centre and genotyping chip of the mother and father.

Appendix 1—table 6

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS, log-transformed outcomes (N=40,949)*.

		Non-genetic estimate^†			MR estimate ^‡			Within-families MR estimate ^‡
Outcome		Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p
Depressive symptoms: log-transformed SMFQ^§ score	Child BMI	0.03	0.01,0.06	0.02	0.31	0.18,0.45	<0.001	0.16	–0.04,0.35	0.12
	Mother’s BMI	0.04	0.03,0.05	<0.001				0.08	0.02,0.14	0.01
	Father’s BMI	0.01	–0.01,0.02	0.56				0.03	–0.05,0.10	0.52
Anxiety symptoms: log-transformed SCARED^¶ score	Child BMI	–0.03	−0.05,–0.01	0.001	–0.04	–0.14,0.05	0.38	–0.00	–0.14,0.13	0.97
	Mother’s BMI	0.00	–0.01,0.01	0.60				–0.02	–0.06,0.02	0.35
	Father’s BMI	–0.00	–0.01,0.01	1.00				–0.01	–0.06,0.05	0.79
ADHD symptoms: log-transformed RS-DBD** score	Child BMI	–0.05	−0.08,–0.02	0.002	0.27	0.13,0.40	<0.001	0.28	0.08,0.49	0.006
	Mother’s BMI	0.03	0.02,0.05	<0.001				0.00	–0.06,0.07	0.90
	Father’s BMI	0.02	–0.00,0.03	0.07				–0.02	–0.10,0.06	0.66
ADHD-inattention symptoms: log-transformed RS-DBD** score, inattention items	Child BMI	–0.04	−0.07,–0.01	0.007	0.22	0.09,0.34	0.001	0.29	0.10,0.47	0.003
	Mother’s BMI	0.03	0.02,0.05	<0.001				0.00	–0.06,0.07	0.92
	Father’s BMI	0.02	0.00,0.03	0.05				–0.06	–0.14,0.02	0.13
ADHD-hyperactivity symptoms: log-transformed RS-DBD** score, hyperactivity items	Child BMI	–0.05	−0.08,–0.01	0.004	0.24	0.10,0.39	0.001	0.18	–0.04,0.40	0.10
	Mother’s BMI	0.02	0.00,0.04	0.01				0.00	–0.07,0.07	1.00
	Father’s BMI	0.01	–0.01,0.03	0.25				0.05	–0.04,0.14	0.29

*

Coefficients represent change in symptoms, log-transformed after adding 1, per 5 kg/m² increase in BMI.
†

Phenotypic models adjust for the child’s sex and birth year, the mother’s parity at the child’s birth, and the mother’s and father’s: educational qualifications, depressive/anxiety and ADHD symptoms, and smoking status during pregnancy. They also adjust for the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
‡

Genetic models adjust for the child’s sex and birth year and the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
§

Short Mood and Feelings Questionnaire.
¶

Screen for Child Anxiety Related Disorders.
**

Parent/Teacher Rating Scale for Disruptive Behaviour Disorders.

Appendix 1—table 7

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS, log-transformed outcomes (N=40,949)*.

		Non-genetic estimate^†			MR estimate ^‡			Within-families MR estimate ^‡
Outcome		Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p
Depressive symptoms: log-transformed SMFQ^§ score	Child BMI	0.03	0.01,0.06	0.02	0.07	–0.04,0.17	0.20	0.02	–0.14,0.17	0.84
	Mother’s BMI	0.04	0.03,0.05	<0.001				0.02	–0.06,0.10	0.67
	Father’s BMI	0.01	–0.01,0.02	0.56				0.05	–0.06,0.15	0.39
Anxiety symptoms: log-transformed SCARED^¶ score	Child BMI	–0.03	−0.05,–0.01	0.001	–0.03	–0.10,0.05	0.49	0.01	–0.10,0.12	0.89
	Mother’s BMI	0.00	–0.01,0.01	0.60				–0.01	–0.07,0.04	0.69
	Father’s BMI	–0.00	–0.01,0.01	1.00				–0.03	–0.10,0.04	0.43
ADHD symptoms: log-transformed RS-DBD** score	Child BMI	–0.05	−0.08,–0.02	0.002	–0.06	–0.17,0.05	0.30	–0.03	–0.19,0.13	0.70
	Mother’s BMI	0.03	0.02,0.05	<0.001				–0.02	–0.10,0.06	0.68
	Father’s BMI	0.02	–0.00,0.03	0.07				–0.01	–0.11,0.09	0.79
ADHD-inattention symptoms: log-transformed RS-DBD** score, inattention items	Child BMI	–0.04	−0.07,–0.01	0.007	–0.03	–0.14,0.07	0.52	–0.05	–0.19,0.10	0.52
	Mother’s BMI	0.03	0.02,0.05	<0.001				0.02	–0.06,0.09	0.64
	Father’s BMI	0.02	0.00,0.03	0.05				–0.01	–0.10,0.09	0.87
ADHD-hyperactivity symptoms: log-transformed RS-DBD** score, hyperactivity items	Child BMI	–0.05	−0.08,–0.01	0.004	–0.07	–0.19,0.04	0.21	–0.00	–0.18,0.17	0.98
	Mother’s BMI	0.02	0.00,0.04	0.01				–0.06	–0.15,0.03	0.22
	Father’s BMI	0.01	–0.01,0.03	0.25				–0.02	–0.13,0.09	0.73

*

Coefficients represent change in symptoms, log-transformed after adding 1, per 5 kg/m² increase in BMI.
†

Phenotypic models adjust for the child’s sex and birth year, the mother’s parity at the child’s birth, and the mother’s and father’s: educational qualifications, depressive/anxiety and ADHD symptoms, and smoking status during pregnancy. They also adjust for the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
‡

Genetic models adjust for the child’s sex and birth year and the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
§

Short Mood and Feelings Questionnaire.
¶

Screen for Child Anxiety Related Disorders.
**

Parent/Teacher Rating Scale for Disruptive Behaviour Disorders.

Appendix 1—table 8

Robustness checks based on SNP-specific associations with child’s BMI* and outcomes: SNPs in adult BMI polygenic score.

	Inverse-variance weighted		MR-Egger: slope		MR-Egger: intercept		MR-Median		MR-Modal
For classic MR models	Beta	p	Beta	p	Beta	p	Beta	p	Beta	p
Depressive symptoms: standardized SMFQ^† score	0.12	<0.001	0.09	0.18	0.00	0.56	0.11	<0.001	0.07	0.42
Anxiety symptoms: standardized SCARED^‡ score	–0.02	0.13	–0.05	0.45	0.00	0.61	–0.01	0.87	0.01	0.92
ADHD symptoms: standardized RS-DBD^§ score	0.10	<0.001	0.02	0.77	0.00	0.19	0.09	0.01	0.07	0.40
ADHD symptoms (inattention): standardized RS-DBD^§ score	0.09	<0.001	–0.02	0.73	0.00	0.07	0.09	0.01	–0.02	0.81
ADHD symptoms (hyperactivity): standardized RS-DBD^§ score	0.08	<0.001	0.05	0.40	0.00	0.61	0.08	0.02	0.05	0.55
	Inverse-variance weighted		MR-Egger: slope		MR-Egger: intercept		MR-Median		MR-Modal
For within-families MR models	Beta	p	Beta	p	Beta	p	Beta	p	Beta	p
Depressive symptoms: standardized SMFQ^† score	0.06	<0.001	0.04	0.67	0.00	0.77	0.07	0.16	0.02	0.83
Anxiety symptoms: standardized SCARED^‡ score	0.00	1.00	0.05	0.58	0.00	0.57	0.03	0.57	0.03	0.76
ADHD symptoms: standardized RS-DBD^§ score	0.09	<0.001	0.07	0.41	0.00	0.80	0.09	0.07	0.13	0.24
ADHD symptoms (inattention): standardized RS-DBD^§ score	0.10	<0.001	0.00	0.97	0.00	0.21	0.10	0.03	0.05	0.63
ADHD symptoms (hyperactivity): standardized RS-DBD^§ score	0.07	<0.001	0.13	0.13	0.00	0.44	0.07	0.14	0.06	0.56

*

In the main analyses, all coefficients are expressed in terms of S.D. change in symptoms per 5 kg/m² increase in BMI. In robustness checks, SNP-exposure associations were taken directly from the relevant GWAS. Coefficients above for BMI-outcome associations are therefore on the scale of kg/m².
†

Short Mood and Feelings Questionnaire.
‡

Screen for Child Anxiety Related Disorders.
§

Parent/Teacher Rating Scale for Disruptive Behaviour Disorders.

Appendix 1—table 9

Robustness checks based on SNP-specific associations with child’s BMI* and outcomes: SNPs in childhood body size polygenic score.

	Inverse-variance weighted		MR-Egger: slope		MR-Egger: intercept		MR-Median		MR-Modal
For classic MR models	Beta	p	Beta	p	Beta	p	Beta	p	Beta	p
Depressive symptoms: standardized SMFQ^† score	0.06	0.03	0.10	0.30	0.00	0.57	0.05	0.52	0.04	0.67
Anxiety symptoms: standardized SCARED^‡ score	–0.02	0.40	0.01	0.90	0.00	0.66	–0.02	0.74	–0.01	0.95
ADHD symptoms: standardized RS-DBD^§ score	–0.04	0.14	–0.02	0.85	0.00	0.75	–0.06	0.36	–0.05	0.65
ADHD symptoms (inattention): standardized RS-DBD^§ score	–0.02	0.47	–0.04	0.64	0.00	0.81	–0.08	0.28	–0.08	0.42
ADHD symptoms (hyperactivity): standardized RS-DBD^§ score	–0.05	0.05	0.01	0.90	0.00	0.42	–0.05	0.48	–0.04	0.68
	Inverse-variance weighted		MR-Egger: slope		MR-Egger: intercept		MR-Median		MR-Modal
For within-families MR models	Beta	p	Beta	p	Beta	p	Beta	p	Beta	p
Depressive symptoms: standardized SMFQ^† score	0.02	0.59	0.05	0.70	0.00	0.75	0.03	0.76	0.04	0.79
Anxiety symptoms: standardized SCARED^‡ score	0.02	0.60	0.07	0.64	0.00	0.69	0.04	0.66	0.05	0.74
ADHD symptoms: standardized RS-DBD^§§ score	–0.02	0.53	0.09	0.49	0.00	0.35	–0.01	0.94	0.03	0.85
ADHD symptoms (inattention): standardized RS-DBD^§ score	–0.04	0.28	0.06	0.65	0.00	0.41	–0.04	0.68	0.01	0.95
ADHD symptoms (hyperactivity): standardized RS-DBD^§ score	0.00	0.98	0.11	0.43	0.00	0.39	0.02	0.80	0.06	0.67

*

In the main analyses, all coefficients are expressed in terms of S.D. change in symptoms per 5 kg/m² increase in BMI. In robustness checks, SNP-exposure associations were taken directly from the relevant GWAS. Coefficients above for BMI-outcome associations are therefore on the scale of kg/m².
†

Short Mood and Feelings Questionnaire.
‡

Screen for Child Anxiety Related Disorders.
§

Parent/Teacher Rating Scale for Disruptive Behaviour Disorders.

Appendix 1—table 10

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS, complete-case analysis*.

		Non-genetic estimate^†			MR estimate ^‡			Within-families MR estimate ^‡
Outcome		Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p
Depressive symptoms: standardized SMFQ ^§ score. N=5,158	Child BMI	0.08	0.00,0.15	0.05	0.38	0.00,0.77	0.05	0.16	–0.35,0.66	0.55
	Mother’s BMI	0.07	0.03,0.11	<0.001				0.10	–0.06,0.26	0.21
	Father’s BMI	0.01	–0.04,0.05	0.79				0.04	–0.15,0.23	0.66
Anxiety symptoms: standardized SCARED ^¶ score. N=5,177	Child BMI	–0.04	–0.12,0.03	0.26	–0.15	–0.54,0.24	0.45	–0.07	–0.62,0.48	0.80
	Mother’s BMI	0.02	–0.02,0.06	0.26				0.06	–0.11,0.22	0.48
	Father’s BMI	0.01	–0.04,0.05	0.69				–0.13	–0.34,0.08	0.24
ADHD symptoms: standardized RS-DBD** ^¶score, ADHD items. N=5,174	Child BMI	–0.03	–0.11,0.04	0.38	0.41	–0.00,0.83	0.05	0.54	0.01,1.08	0.04
	Mother’s BMI	0.09	0.05,0.12	<0.001				–0.01	–0.16,0.15	0.93
	Father’s BMI	–0.01	–0.05,0.03	0.60				–0.09	–0.29,0.12	0.41
ADHD-inattention symptoms: standardized RS-DBD** score, inattention items. N=5,171	Child BMI	–0.02	–0.10,0.05	0.55	0.44	0.04,0.85	0.03	0.73	0.20,1.25	0.01
	Mother’s BMI	0.09	0.05,0.12	<0.001				–0.02	–0.18,0.14	0.84
	Father’s BMI	–0.00	–0.05,0.04	0.83				–0.18	–0.39,0.03	0.09
ADHD-hyperactivity symptoms: standardized RS-DBD** score, hyperactivity items. N=5,167	Child BMI	–0.04	–0.11,0.03	0.29	0.28	–0.13,0.70	0.18	0.21	–0.32,0.75	0.43
	Mother’s BMI	0.07	0.03,0.11	0.001				0.01	–0.15,0.17	0.87
	Father’s BMI	–0.01	–0.06,0.03	0.51				0.03	–0.17,0.24	0.75

*

Coefficients represent S.D. change in symptoms per 5 kg/m² increase in BMI.
†

Phenotypic models adjust for the child’s sex and birth year, the mother’s parity at the child’s birth, and the mother’s and father’s: educational qualifications, depressive/anxiety and ADHD symptoms, and smoking status during pregnancy. They also adjust for the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
‡

Genetic models adjust for the child’s sex and birth year and the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
§

Short Mood and Feelings Questionnaire
¶

Screen for Child Anxiety Related Disorders
**

Parent/Teacher Rating Scale for Disruptive Behaviour Disorders.

Appendix 1—table 11

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS, complete-case analysis*.

		Non-genetic estimate^†			MR estimate^‡			Within-families MR estimate^‡
Outcome		Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p
Depressive symptoms: standardized SMFQ^§ score N=5,158	Child BMI^a	0.08	0.00,0.15	0.05	0.13	–0.15,0.42	0.37	0.10	–0.34,0.54	0.65
	Mother’s BMI	0.07	0.03,0.11	<0.001				–0.06	–0.26,0.14	0.57
	Father’s BMI	0.01	–0.04,0.05	0.79				0.10	–0.20,0.40	0.52
Anxiety symptoms: standardized SCARED^¶ score N=5,177	Child BMI	–0.04	–0.12,0.03	0.26	–0.03	–0.32,0.27	0.85	0.06	–0.37,0.48	0.79
	Mother’s BMI	0.02	–0.02,0.06	0.26				0.02	–0.19,0.24	0.85
	Father’s BMI	0.01	–0.04,0.05	0.69				–0.13	–0.43,0.18	0.42
ADHD symptoms: standardized RS-DBD** score, ADHD items N=5,174	Child BMI	–0.03	–0.11,0.04	0.38	0.00	–0.29,0.30	0.98	0.13	–0.31,0.56	0.57
	Mother’s BMI	0.09	0.05,0.12	<0.001				–0.05	–0.25,0.15	0.61
	Father’s BMI	–0.01	–0.05,0.03	0.60				–0.09	–0.40,0.22	0.56
ADHD-inattention symptoms: standardized RS-DBD** score, inattention items N=5,171	Child BMI	–0.02	–0.10,0.05	0.55	–0.00	–0.29,0.29	0.99	0.13	–0.29,0.55	0.55
	Mother’s BMI	0.09	0.05,0.12	<0.001				0.04	–0.17,0.24	0.72
	Father’s BMI	–0.00	–0.05,0.04	0.83				–0.20	–0.51,0.11	0.20
ADHD-hyperactivity symptoms: standardized RS-DBD** score, hyperactivity items N=5,167	Child BMI	–0.04	–0.11,0.03	0.29	0.00	–0.30,0.30	0.99	0.10	–0.35,0.55	0.67
	Mother’s BMI	0.07	0.03,0.11	0.001				–0.14	–0.34,0.06	0.18
	Father’s BMI	–0.01	–0.06,0.03	0.51				0.03	–0.28,0.34	0.84

*

Coefficients represent S.D. change in symptoms per 5 kg/m² increase in BMI.
†

Phenotypic models adjust for the child’s sex and birth year, the mother’s parity at the child’s birth, and the mother’s and father’s: educational qualifications, depressive/anxiety and ADHD symptoms, and smoking status during pregnancy. They also adjust for the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
‡

Genetic models adjust for the child’s sex and birth year and the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
§

Short Mood and Feelings Questionnaire.
¶

Screen for Child Anxiety Related Disorders.
**

Parent/Teacher Rating Scale for Disruptive Behaviour Disorders.

Appendix 1—table 12

Multivariable-adjusted associations* of BMI quintiles with symptoms of depression, anxiety, and ADHD at age 8 in MoBa.

	Depressive symptoms: standardized SMFQ† score		Anxiety symptoms: standardized SCARED ‡ score		ADHD symptoms: standardized RS-DBD § score, ADHD items		ADHD-inattention symptoms: standardized RS-DBD § score, inattention items		ADHD-hyperactivity symptoms: standardized RS-DBD § score, hyperactivity items
BMI quintile	Beta ^¶ (95% CI)	p	Beta ^¶ (95% CI)	p	Beta ^¶ (95% CI)	p	Beta ^¶ (95% CI)	p	Beta ^¶ (95% CI)	p
1	0.00 (-0.04,0.04)	0.99	0.04 (0.00,0.09)	0.04	0.05 (0.01,0.09)	0.01	0.05 (0.01,0.09)	0.02	0.04 (-0.00,0.08)	0.05
2	–0.01 (-0.05,0.03)	0.70	0.02 (-0.03,0.06)	0.47	0.02 (-0.02,0.06)	0.29	0.02 (-0.02,0.06)	0.38	0.02 (-0.02,0.06)	0.30
3 (ref)	1		1		1		1		1
4	0.01 (-0.03,0.05)	0.62	–0.03 (-0.07,0.01)	0.16	–0.01 (-0.04,0.03)	0.66	–0.01 (-0.05,0.02)	0.54	–0.00 (-0.04,0.03)	0.87
5	0.04 (0.00,0.08)	0.03	–0.03 (-0.07,0.01)	0.09	–0.02 (-0.06,0.02)	0.27	–0.01 (-0.05,0.03)	0.51	–0.03 (-0.06,0.01)	0.20

*

Models adjust for the child’s sex and birth year, the mother’s parity at the child’s birth, and the mother’s and father’s: educational qualifications, depressive/anxiety and ADHD symptoms, and smoking status during pregnancy. They also adjust for the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
†

Short Mood and Feelings Questionnaire.
‡

Screen for Child Anxiety Related Disorders.
§

Parent/Teacher Rating Scale for Disruptive Behaviour Disorders.
¶

Coefficients represent S.D. difference in symptoms between quintiles of child’s BMI.

Appendix 1—table 13

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS, genetic models adjusted for parental education (N=40,949)*.

		MR estimate^†			Within-families MR estimate^†
Outcome		Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p
Depressive symptoms: standardized SMFQ^‡ score	Child BMI	0.38	0.19,0.58	<0.001	0.26	–0.01,0.53	0.06
	Mother’s BMI				0.09	–0.00,0.17	0.05
	Father’s BMI				–0.00	–0.11,0.11	0.97
Anxiety symptoms: standardized SCARED^§ score	Child BMI	–0.08	–0.26,0.11	0.43	0.01	–0.25,0.27	0.95
	Mother’s BMI				–0.04	–0.12,0.05	0.40
	Father’s BMI				–0.03	–0.14,0.08	0.64
ADHD symptoms: standardized RS-DBD ^¶ score, ADHD items	Child BMI	0.27	0.09,0.45	0.003	0.37	0.10,0.64	0.007
	Mother’s BMI				–0.03	–0.12,0.06	0.52
	Father’s BMI				–0.05	–0.16,0.06	0.37
ADHD-inattention symptoms: standardized RS-DBD^¶ score, inattention items	Child BMI	0.25	0.07,0.42	0.007	0.39	0.13,0.66	0.004
	Mother’s BMI				–0.02	–0.11,0.07	0.64
	Father’s BMI				–0.10	–0.21,0.01	0.08
ADHD-hyperactivity symptoms: standardized RS-DBD^¶ score, hyperactivity items	Child BMI	0.24	0.06,0.42	0.009	0.27	0.00,0.55	0.05
	Mother’s BMI				–0.03	–0.12,0.06	0.49
	Father’s BMI				0.01	–0.10,0.12	0.85

*

Coefficients represent S.D. change in symptoms per 5 kg/m² increase in BMI.
†

Models adjust for the child’s sex and birth year and the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
‡

Short Mood and Feelings Questionnaire.
§

Screen for Child Anxiety Related Disorders.
¶

Parent/Teacher Rating Scale for Disruptive Behaviour Disorders.

Appendix 1—table 14

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS, genetic models adjusted for parental education (N=40,949)*.

		MR estimate^†			Within-families MR estimate^†
Outcome		Beta (per 5 kg/m²)	CI	p	Beta (per 5 kg/m²)	CI	p
Depressive symptoms: standardized SMFQ^‡ score	Child BMI	0.07	–0.07,0.22	0.33	0.01	–0.20,0.23	0.90
	Mother’s BMI				0.02	–0.10,0.13	0.76
	Father’s BMI				0.05	–0.09,0.20	0.48
Anxiety symptoms: standardized SCARED^§ score	Child BMI	–0.03	–0.18,0.11	0.65	0.03	–0.18,0.23	0.81
	Mother’s BMI				–0.02	–0.13,0.09	0.76
	Father’s BMI				–0.06	–0.19,0.08	0.44
ADHD symptoms: standardized RS-DBD ^¶ score, ADHD items	Child BMI	–0.08	–0.22,0.06	0.27	–0.03	–0.23,0.16	0.75
	Mother’s BMI				–0.03	–0.13,0.07	0.50
	Father’s BMI				–0.02	–0.15,0.11	0.79
ADHD-inattention symptoms: standardized RS-DBD^¶ score, inattention items	Child BMI	–0.05	–0.20,0.10	0.52	–0.06	–0.25,0.14	0.57
	Mother’s BMI				0.02	–0.08,0.12	0.74
	Father’s BMI				–0.01	–0.14,0.12	0.87
ADHD-hyperactivity symptoms: standardized RS-DBD^¶ score, hyperactivity items	Child BMI	–0.10	–0.23,0.04	0.18	–0.00	–0.21,0.21	1.00
	Mother’s BMI				–0.08	–0.19,0.03	0.15
	Father’s BMI				–0.02	–0.15,0.12	0.77

*

Coefficients represent S.D. change in symptoms per 5 kg/m² increase in BMI.
†

Models adjust for the child’s sex and birth year and the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry.
‡

Short Mood and Feelings Questionnaire.
§

Screen for Child Anxiety Related Disorders.
¶

Parent/Teacher Rating Scale for Disruptive Behaviour Disorders.

Author response table 1

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, using adult and childhood body size PGS with a p-value threshold of 1.

		Adult BMI PGS, p-value threshold of 1^a						Childhood body size PGS, p-value threshold of 1^a
		MR estimate^b			Within-families MR estimate^b			MR estimate^b			Within-families MR estimate^b
		Beta	CI	p	Beta	CI	p	Beta	CI	p	Beta	CI	p
Depressive symptoms: SMFQ^c score	Child BMI^a	0.43	0.26,0.60	<0.001	0.31	0.06,0.57	0.02	0.1	–0.05,0.24	0.18	–0.06	–0.26,0.14	0.57
	Mother’s BMI				0.04	–0.03,0.12	0.27				0.10	–0.01,0.21	0.09
	Father’s BMI				0.03	–0.07,0.14	0.52				0.10	–0.05,0.25	0.18
Anxiety symptoms: SCARED^d score	Child BMI	–0.25	–0.42,0.08	0.004	–0.34	−0.59,–0.10	0.005	–0.1	–0.24,0.04	0.16	–0.24	−0.43,–0.05	0.01
	Mother’s BMI				0.03	–0.05,0.10	0.48				0.12	0.01,0.23	0.03
	Father’s BMI				0.04	–0.06,0.14	0.42				0.05	–0.09,0.19	0.48
ADHD symptoms: RS-DBD^e score	Child BMI	0.48	0.31,0.65	<0.001	0.69	0.43,0.95	<0.001	–0.09	–0.23,0.06	0.24	–0.15	–0.35,0.05	0.15
	Mother’s BMI				–0.05	–0.13,0.03	0.19				0.07	–0.04,0.18	0.24
	Father’s BMI				–0.10	–0.20,0.00	0.06				0.01	–0.13,0.15	0.93
ADHD-inattention symptoms: RS-DBD^e score, inattention items	Child BMI	0.44	0.26,0.61	<0.001	0.65	0.39,0.92	<0.001	–0.07	–0.21,0.08	0.37	–0.15	–0.35,0.05	0.15
	Mother’s BMI				–0.06	–0.14,0.02	0.13				0.10	–0.01,0.21	0.09
	Father’s BMI				–0.09	–0.19,0.01	0.08				–0.01	–0.15,0.14	0.93
ADHD-hyperactivity symptoms: RS-DBD^e score, hyperactivity items	Child BMI	0.42	0.25,0.60	<0.001	0.59	0.32,0.85	<0.001	–0.09	–0.24,0.06	0.24	–0.12	–0.33,0.08	0.25
	Mother’s BMI				–0.03	–0.11,0.05	0.42				0.02	–0.09,0.13	0.70
	Father’s BMI				–0.08	–0.19,0.02	0.12				0.02	–0.12,0.16	0.80
^aCoefficients represent change in symptoms, log-transformed after adding 1, per 5 kg/m² increase in BMI. ^bGenetic models adjust for child’s sex, genotyping batch, and the first 20 principal components of ancestry. ^cShort Mood and Feelings Questionnaire. ^dScreen for Child Anxiety Related Disorders. ^eParent/Teacher Rating Scale for Disruptive Behaviour Disorders.

Author response table 2

Non-genetic associations of BMI and symptoms of depression, anxiety, and ADHD at age 8
		Full adjustment^b			Less adjustment^c
		Beta	CI	p	Beta	CI	p
Depressive symptoms: SMFQ^d score	Child BMI^a	0.05	0.01,0.09	0.02	0.05	0.01,0.09	0.02
	Mother’s BMI	0.05	0.03,0.07	<0.001	0.05	0.03,0.07	<0.001
	Father’s BMI	0.01	–0.02,0.03	0.67	0.01	–0.02,0.03	0.58
Anxiety symptoms: SCARED^e score	Child BMI	–0.07	−0.11,–0.03	0.001	–0.07	−0.11,–0.03	<0.001
	Mother’s BMI	0.01	–0.01,0.03	0.47	0.01	–0.01,0.03	0.45
	Father’s BMI	–0.00	–0.02,0.02	0.89	–0.00	–0.02,0.02	0.91
ADHD symptoms: RS-DBD^f score	Child BMI	–0.07	−0.11,–0.03	0.001	–0.07	−0.10,–0.03	0.001
	Mother’s BMI	0.04	0.02,0.06	<0.001	0.04	0.02,0.06	<0.001
	Father’s BMI	0.02	–0.00,0.04	0.10	0.02	–0.00,0.05	0.07
^aCoefficients represent S.D. change in symptoms per 5 kg/m² increase in BMI. ^bAdjusted for child’s sex, mother’s and father’s educational qualifications, mother’s and father’s depressive/anxiety symptoms and ADHD symptoms, mother’s and father’s smoking status during pregnancy, and maternal parity, and the child’s, mother’s, and father’s genotyping centre, genotyping chip, and first 20 principal components of ancestry. ^cAdjusted for the child’s sex, mother’s and father’s educational qualifications, mother’s and father’s depressive/anxiety symptoms and ADHD symptoms, mother’s and father’s smoking status during pregnancy, and maternal parity. ^dShort Mood and Feelings Questionnaire. ^eScreen for Child Anxiety Related Disorders. ^fParent/Teacher Rating Scale for Disruptive Behaviour Disorders

Additional files

Supplementary file 1 (a) SNPs used in the polygenic score for adult BMI. (b) SNPs used in the polygenic score for childhood body size BMI. (c) SNPs used in the polygenic score for depression. (d) SNPs used in the polygenic score for ADHD.: https://cdn.elifesciences.org/articles/74320/elife-74320-supp1-v1.xlsx
Download elife-74320-supp1-v1.xlsx
Transparent reporting form: https://cdn.elifesciences.org/articles/74320/elife-74320-transrepform1-v1.pdf
Download elife-74320-transrepform1-v1.pdf
Reporting standard 1 Strobe checklist.: https://cdn.elifesciences.org/articles/74320/elife-74320-repstand1-v1.docx
Download elife-74320-repstand1-v1.docx

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Amanda M Hughes
Eleanor Sanderson
Tim Morris
Ziada Ayorech
Martin Tesli
Helga Ask
Ted Reichborn-Kjennerud
Ole A Andreassen
Per Magnus
Øyvind Helgeland
Stefan Johansson
Pål Njølstad
George Davey Smith
Alexandra Havdahl
Laura D Howe
Neil M Davies

(2022)

Body mass index and childhood symptoms of depression, anxiety, and attention-deficit hyperactivity disorder: A within-family Mendelian randomization study

eLife 11:e74320.

https://doi.org/10.7554/eLife.74320

Figures

Bias in Mendelian randomization studies which do not account for parental genotype.

BMI and child’s depressive, anxiety, and ADHD symptoms, using a polygenic score for adult BMI (N=40,949 trios).

BMI and child’s depressive, anxiety, and ADHD symptoms, using a polygenic score for childhood body size (N=40,949 trios).

Flow chart of inclusion and exclusion of MoBa participants into the study sample.

Associations of child’s BMI polygenic scores with ancestry.

Associations of child’s BMI polygenic scores with ancestry, adjusted for parental polygenic scores.

Tables

Descriptive characteristics of analytic sample (N=40,949)*.

Descriptive statistics of full MoBa sample (N=113,691)*.

Descriptive statistics of analytic sample (N=40,949)*, unimputed data.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS (N=40,949)*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS (N=40,949)*.

Associations of phenotypes and polygenic scores within parental pairs*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS, log-transformed outcomes (N=40,949)*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS, log-transformed outcomes (N=40,949)*.

Robustness checks based on SNP-specific associations with child’s BMI* and outcomes: SNPs in adult BMI polygenic score.

Robustness checks based on SNP-specific associations with child’s BMI* and outcomes: SNPs in childhood body size polygenic score.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS, complete-case analysis*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS, complete-case analysis*.

Multivariable-adjusted associations* of BMI quintiles with symptoms of depression, anxiety, and ADHD at age 8 in MoBa.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS, genetic models adjusted for parental education (N=40,949)*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS, genetic models adjusted for parental education (N=40,949)*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, using adult and childhood body size PGS with a p-value threshold of 1.

Additional files

Supplementary file 1

Transparent reporting form

Reporting standard 1

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Bias in Mendelian randomization studies which do not account for parental genotype.

BMI and child’s depressive, anxiety, and ADHD symptoms, using a polygenic score for adult BMI (N=40,949 trios).

BMI and child’s depressive, anxiety, and ADHD symptoms, using a polygenic score for childhood body size (N=40,949 trios).

Flow chart of inclusion and exclusion of MoBa participants into the study sample.

Associations of child’s BMI polygenic scores with ancestry.

Associations of child’s BMI polygenic scores with ancestry, adjusted for parental polygenic scores.

Descriptive characteristics of analytic sample (N=40,949)*.

Descriptive statistics of full MoBa sample (N=113,691)*.

Descriptive statistics of analytic sample (N=40,949)*, unimputed data.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS (N=40,949)*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS (N=40,949)*.

Associations of phenotypes and polygenic scores within parental pairs*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS, log-transformed outcomes (N=40,949)*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS, log-transformed outcomes (N=40,949)*.

Robustness checks based on SNP-specific associations with child’s BMI* and outcomes: SNPs in adult BMI polygenic score.

Robustness checks based on SNP-specific associations with child’s BMI* and outcomes: SNPs in childhood body size polygenic score.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS, complete-case analysis*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS, complete-case analysis*.

Multivariable-adjusted associations* of BMI quintiles with symptoms of depression, anxiety, and ADHD at age 8 in MoBa.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, adult BMI PGS, genetic models adjusted for parental education (N=40,949)*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, childhood body size PGS, genetic models adjusted for parental education (N=40,949)*.

BMI and symptoms of depression, anxiety, and ADHD at age 8 in MoBa, using adult and childhood body size PGS with a p-value threshold of 1.

Supplementary file 1

Transparent reporting form

Reporting standard 1

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)