Extended Data Table 1.

Phenotypes tested for association with having a pathogenic de novo mutation.

Category	Phenotype	Type	Value	95% CI	P-value
Post-natal	abnormal cranial MRI	Odds ratio	1.365	1.125 – 1.656	0.002
	feeding problems	Odds ratio	1.176	1.01 – 1.369	0.039
	neonatal intensive care	Odds ratio	0.896	0.762 – 1.054	0.190
	anticonvulsant drugs	Odds ratio	0.582	0.246 – 1.377	0.270
Pre-natal	bleeding	Odds ratio	0.892	0.714 – 1.114	0.346
	maternal illness	Odds ratio	0.908	0.764 – 1.079	0.278
	maternal diabetes	Odds ratio	0.787	0.504 – 1.229	0.341
	abnormal scan	Odds ratio	0.839	0.692 – 1.017	0.078
	assisted reproduction	Odds ratio	0.868	0.554 – 1.36	0.584
	increased nuchal translucency	Odds ratio	1.432	0.903 – 2.271	0.126
Family history	consanguinity	Odds ratio	0.234	0.138 – 0.397	8.0 x 10-11
	similar phenotype parents	Odds ratio	0.295	0.184 – 0.474	5.7 x 10-9
	similar phenotype relatives	Odds ratio	0.553	0.402 – 0.761	1.5 x 10-4
	similar phenotype siblings	Odds ratio	0.311	0.23 – 0.421	7.3 x 10-18
	only patient affected	Odds ratio	2.478	2.001 – 3.068	3.9 x 10-19
	X-linked inheritance	Odds ratio	0.839	0.436 – 1.613	0.752
	Multiple births	Beta	0.043	-0.058 – 0.144	0.403
	History of pregnancy loss	Beta	-0.039	-0.155 – 0.078	0.516
Developmental milestones	first words	Beta	0.205	0.081 – 0.328	0.001
	walked independently	Beta	0.125	0.016 – 0.235	0.025
	sat independently	Beta	0.050	-0.069 – 0.17	0.408
	social smile	Beta	0.072	-0.066 – 0.211	0.305
Growth	height	Beta	0.008	-0.111 – 0.126	0.897
	birthweight	Beta	-0.018	-0.135 – 0.098	0.756
	OFC	Beta	-0.094	-0.215 – 0.026	0.125
	weight	Beta	-0.331	-1.278 – 0.615	0.493
Age	age at assessment	Beta	0.116	0.015 – 0.217	0.025
	gestation	Beta	0.079	-0.033 – 0.19	0.167
	father's age	Beta	0.137	0.027 – 0.247	0.015
	mother's age	Beta	0.108	-0.003 – 0.219	0.056
Other	phenotypic terms (n)	Beta	0.104	0.004 – 0.203	0.041
	autozygosity length	Beta	-0.185	-0.254 – -0.115	1.6 x 10-7
	sex (male)	Odds ratio	0.750	0.646 – 0.87	1.6 x 10-4