Table 1 Genes with recurrent deleterious gDNMs in BD and other neuropsychiatric/developmental disorders.

Gene	pLI	gDNM count^a					gDNM enrichment
		BD	SCZ	ASD	DD	Control	BD (N = 354)	BD + SCZ + ASD (N = 9623)		BD + SCZ + ASD + DD (N = 40,681)
		(N = 354)	(N = 2839)	(N = 6430)	(N = 31,058)	(N = 2179)	Uncorrected P value^b	gDNM count total^a	Uncorrected P value^b	gDNM count total^a	Uncorrected P value^b
Genes with multiple deleterious gDNMs in BD
XKR6	0.9971	2 (0.2)	1 (0.1)	1 (1.0)	7 (1.6)	0	1.13 × 10⁻⁴	4 (1.3)	8.58 × 10⁻⁴	11 (2.9)	2.24 × 10⁻⁶
MRC2	0.9964	2 (0.2)	0	0	3 (3.0)	0	5.47 × 10⁻⁴	2 (0.2)	0.231	5 (3.2)	0.341
Constrained genes with LoF gDNMs in BD and other disorders
KMT2C	1	1	2	4	14	0	0.0148	7	2.48 × 10⁻⁷	21	3.03 × 10⁻¹⁶
SMARCC2	1	1	1	2	0	0	0.00404	4	5.62 × 10⁻⁶	4	0.00135
XPO4	1	1	0	1	1	0	0.00378	2	0.00496	3	0.00997
TNRC18	0.9999	1	0	1	0	0	0.00542	2	0.00991	2	0.130
KLF4	0.9743	1	0	0	1	0	0.00125	1	0.0334	2	0.00937
ATP2B2	0.9997	1	0	0	1	0	0.00330	1	0.0861	2	0.0564
CCAR1	0.9999	1	0	0	1	0	0.00436	1	0.112	2	0.0909
RAPGEF2	1	1	0	0	1	1	0.00458	1	0.117	2	0.0988

Boldface indicates genes with exome-wide significance defined as P < 2.74 × 10⁻⁶ (= 0.05/18,271).
ASD autism spectrum disorder, BD bipolar disorder, DD developmental disorder, gDNM germline de novo mutation, LoF loss of function, pLI probability of being LoF-intolerant, SCZ schizophrenia.
^aFor genes with multiple deleterious gDNMs in BD and other disorders, the total numbers of deleterious gDNMs with the numbers of LoF and damaging missense/inframe indel gDNMs in the parenthesis are shown. For constrained genes with LoF gDNMs in BD and other disorders, the numbers of LoF gDNMs are shown.
^bFor genes with multiple deleterious gDNMs in BD and other disorders, P values were calculated by comparing the observed and expected numbers of deleterious gDNMs. For constrained genes with LoF gDNMs in BD and other disorders, P values were calculated by comparing the observed and expected numbers of LoF gDNMs. The listed genes are limited to those also hit by deleterious/LoF gDNMs in other neuropsychiatric/developmental disorders than BD (i.e., SCZ, ASD, or DD in this Table, Supplementary Table 1).

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