Integration of genetic, transcriptomic, and clinical data provides insight into 16p11.2 and 22q11.2 CNV genes

Vysotskiy, Mikhail; Zhong, Xue; Miller-Fleming, Tyne W.; Zhou, Dan; Cox, Nancy J.; Weiss, Lauren A.

doi:10.1186/s13073-021-00972-1

Table 2 Selected 22q11.2 gene associations with PheWAS traits

From: Integration of genetic, transcriptomic, and clinical data provides insight into 16p11.2 and 22q11.2 CNV genes

Gene	PheWAS trait	P value	Reason for inclusion
TUBA8	Acute reaction to stress	0.0006	Brain-related
	Delirium dementia and amnestic and other cognitive disorders	0.0015	Brain-related
	Attention deficit hyperactivity disorder	0.0031	Brain-related
USP18	Aphasia	0.00066	Brain-related
	Pulmonary collapse; interstitial and compensatory emphysema	0.00091	Del
	Arrhythmia (cardiac) NOS	0.0026	Del
GGT3P	Endocrine and metabolic disturbances of fetus and newborn	0.00068	Del
	Respiratory failure	0.0015	Del
	Memory loss	0.016	Brain-related
DGCR6	Diseases of the larynx and vocal cords	0.0014	Del
DGCR6	Tobacco use disorder	0.0086	Brain-related
PRODH	Gout and other crystal arthropathies^a	1.3 × 10⁻⁵	PheWS
	Diseases of the larynx and vocal cords	0.005893	Del
	Voice disturbance	0.00801	Del
DGCR9	Gastrointestinal hemorrhage	0.00016	Del
TSSK1A	Hypoparathyroidism	0.0011	Del
TSSK1A	Disorders of parathyroid gland	0.0029	Del
SLC25A1	Acute upper respiratory infections of multiple or unspecified sites	0.00015	Del
CLTCL1	Anxiety, phobic and dissociative disorders	0.0054	Brain-related
C22orf39	Other disorders of tympanic membrane	0.0051	Del
C22orf39	Abnormality of gait	0.0092	Dup, brain-related
CDC45	Hypoparathyroidism	0.00061	Del
	Impulse control disorder	0.0035	Brain-related
	Pervasive developmental disorders	0.011	Dup, brain-related
CLDN5	Eustachian tube disorders	0.0078	Del
TBX1	Curvature of spine	0.00083	Del
	Agorophobia, social phobia, and panic disorder	0.0013	Brain-related
	Personality disorders	0.0043	Brain-related
GNB1L	Delirium dementia and amnestic and other cognitive disorders	0.0023	Brain-related
	Heart valve disorders	0.0029	Del
	Dementias	0.0047	Brain-related
	Acute upper respiratory infections of multiple or unspecified sites	0.0071	Del
	Tachycardia NOS	0.0074	Del
ARVCF	Obsessive-compulsive disorders	0.0024	Brain-related
	Diseases of the larynx and vocal cords	0.0041	Del
	Chromosomal anomalies	0.0075	Del/dup
	Hypoparathyroidism	0.0094	Del
TANGO2	Autism	0.0011	Dup, brain-related
	Tension headache	0.002	Drain-related
	Antisocial/borderline personality disorder	0.0028	Drain-related
	Epilepsy, recurrent seizures, convulsions	0.0049	Del/dup, brain-related
DGCR8	Dependence on respirator [Ventilator] or supplemental oxygen	0.00059	Del
DGCR8	Hallucinations	0.0061	Brain-related
TRMT2A	Other specified nonpsychotic and/or transient mental disorders	0.0033	Brain-related
TRMT2A	Alteration of consciousness	0.0061	Brain-related
RANBP1	Bariatric surgery	0.00034	Brain-related
	Obsessive-compulsive disorders	0.0011	Brain-related
	Pulmonary insufficiency or respiratory failure following trauma and surgery	0.0026	Del
	Acute upper respiratory infections of multiple or unspecified sites	0.0035	Del
ZDHHC8	Autism	0.0013	Dup, brain-related
	Tension headache	0.0035	Brain-related
	Acute reaction to stress	0.0049	Brain-related
RTN4R	Heart valve disorders	0.0035	Del
	Swelling, mass, or lump in head and neck [Space-occupying lesion, intracranial NOS]	0.0044	Brain-related
	Tension headache	0.0065	Brain-related
	Epilepsy, recurrent seizures, convulsions	0.0084	Del/dup, brain-related
DGCR6L	Disorders of fluid, electrolyte, and acid-base balance	0.0065	Del
DGCR6L	Other persistent mental disorders due to conditions classified elsewhere	0.0077	Brain-related
USP41	Impacted cerumen	0.0026	Del
	Esophagitis, GERD and related diseases	0.006	Del
	Alzheimer's disease	0.0072	Brain-related
ZNF74	Septicemia	0.00061	Del
	Mood disorders	0.0053	Brain-related
	Heart valve disorders	0.0057	Del
SCARF2	Mood disorders^{a, c}	1.3 × 10⁻⁵	Brain-related, PheWS
	Depression	0.00014	Brain-related
	Schizophrenia	0.00027	Brain-related
	Blood in stool	0.00071	Del
	Obsessive-compulsive disorders	0.001	Brain-related
	Alteration of consciousness	0.0011	Brain-related
	Schizophrenia and other psychotic disorders	0.003	Brain-related
	Major depressive disorder	0.0033	Brain-related
	Respiratory conditions of fetus and newborn	0.0035	Del
KLHL22	Premature beats	0.00013	Del
	Valvular heart disease/ heart chambers	0.0051	Del
	Overweight, obesity and other hyperalimentation	0.0064	Brain-related
	Mood disorders	0.01	Brain-related
	Heart transplant/surgery	0.011	Del
	Posttraumatic stress disorder	0.012	Brain-related
	Obsessive-compulsive disorders	0.012	Brain-related
KRT18P5	Acute posthemorrhagic anemia	0.00048	Del
KRT18P5	Other persistent mental disorders due to conditions classified elsewhere	0.0016	Brain-related
MED15	Other upper respiratory disease	0.0019	Del
MED15	Mood disorders	0.0120	Brain-related
SMPD4P1	Other disorders of intestine	0.001	Del
	Acidosis	0.0039	Del
	Acid-base balance disorder	0.0054	Del
	Renal failure	0.0059	Del
POM121L4P	Acute reaction to stress	0.0022	Brain-related
POM121L4P	Convulsions	0.0072	Del, brain-related
PI4KA	Disorders of iris and ciliary body^a	1.1 × 10⁻⁷	PheWS
	Muscular calcification and ossification^a	7.3 × 10⁻⁶	PheWS
	Disorders resulting from impaired renal function^a	2.2 × 10⁻⁵	PheWS
	Stricture/obstruction of ureter^a	3.1 × 10⁻⁵	PheWS
	Disorders of calcium/phosphorus metabolism	5.7 × 10⁻⁵	Del
	Renal failure	0.0007	Del
SERPIND1	Other anemias	0.00044	Del
	Essential hypertension	0.00045	Del
	Renal failure	0.0009	Del
	Acidosis	0.001	Del
	Septicemia	0.0011	Del
SNAP29	Curvature of spine	0.0015	Del
SNAP29	Morbid obesity	0.0045	Brain-related
AIFM3	Renal failure^a	2.3 × 10⁻⁵	Del, PheWS
	Pulmonary collapse; interstitial and compensatory emphysema	0.0053	Del
	Mood disorders^c	0.006	Brain-related
LZTR1	Malignant neoplasm, other^a	1.4 × 10⁻⁵	PheWS
	Renal failure	0.00077	Del
	Septicemia	0.0014	Del
	Obsessive-compulsive disorders	0.0018	Brain-related
	Esophagitis, GERD and related diseases	0.0054	Del
	Pulmonary collapse; interstitial and compensatory emphysema	0.0056	Del
TUBA3FP	Psychogenic disorder	0.0017	Brain-related
TUBA3FP	Hypothyroidism NOS	0.0074	Del
P2RX6	Morbid obesity	0.00012	Brain-related
	Other perinatal conditions of fetus or newborn	0.00022	Del
	Renal failure	0.00067	Del
	Eating disorder	0.0065	Brain-related
P2RX6P	Morbid obesity^b	0.00043	Brain-related
	Paroxysmal tachycardia, unspecified	0.0014	Del
	Eating disorder	0.0072	Brain-related
BCRP2	Disorders of parathyroid gland	0.0078	Del
GGT2	Depression	0.0038	Brain-related
	Hypovolemia	0.0043	Del
	Chromosomal anomalies and genetic disorders	0.0059	Del/dup
	Mood disorders	0.0064	Brain-related
POM121L8P	Immunity deficiency	0.0063	Del
HIC2	Bacterial infection NOS	0.00023	Del
	Mood disorders^c	0.000464	Brain-related
	Tension headache	0.00069	Brain-related
	Swelling, mass, or lump in head and neck [Space-occupying lesion, intracranial NOS]	0.00091	Brain-related
	Esophagitis, GERD and related diseases	0.002	Del
	Pleurisy; pleural effusion	0.0023	Del
	Posttraumatic stress disorder	0.0028	Brain-related
	Pervasive developmental disorders	0.0031	Dup, brain-related
TMEM191C	Other CNS infection and poliomyelitis^a	7.2 × 10⁻⁶	PheWS
	Eustachian tube disorders	0.0022	Del
	Renal failure	0.0029	Del
	Septicemia	0.0038	Del
	Bacteremia	0.0073	Del
	Diseases of hard tissues of teeth	0.008431	Del
RIMBP3C	Cellulitis and abscess of oral soft tissues^a	1.8 × 10⁻⁵	PheWS
	Pulmonary insufficiency or respiratory failure following trauma and surgery	0.00047	Del
	Obsessive-compulsive disorders	0.0018	Brain-related
UBE2L3	Acute reaction to stress	0.0019	Brain-related
YDJC	Swelling, mass, or lump in head and neck [Space-occupying lesion, intracranial NOS]	0.00025	Brain-related
	Symptoms involving head and neck	0.00072	Brain-related
	Ill-defined descriptions and complications of heart disease	0.0027	Del
	Speech and language disorder	0.0042	Del, brain-related
CCDC116	Abdominal aortic aneurysm^a	1.9 × 10⁻⁶	PheWS
CCDC116	Respiratory conditions of fetus and newborn	0.0032	Del
PPIL2	Arrhythmia (cardiac) NOS	0.006	Del

Possible reasons for inclusion are (1) del, dup, or del/dup: trait is over-represented in 16p11.2 deletion carriers, duplication carriers, or both (P < 2.8 × 10⁻⁵); (2) brain-related trait; (3) PheWS, phenome-wide significant
^aPhenome-wide significant gene-trait pair (P < 3.3 × 10⁻⁵)
^bNot significant after conditional analysis
^cIn an independent dataset, this brain-related gene-trait pair reached P < 0.05 and was in the top 5% of genes associated with this trait overall

Back to article page

ISSN: 1756-994X

Contact us

Submission enquiries: editorial@genomemedicine.com
General enquiries: info@biomedcentral.com

Genome Medicine

Contact us