Table 4 ∣.

Replication of novel associations in the Geisinger MyCode cohort

Binary traits
Trait	Gene	Carriers	OR [95% CI]	P-value
Diabetes type 2	GIGYF1	152	3.18 [2.22, 4.54]	1.98 x 10−9
	CCAR2	24	0.75 [0.24, 2.33]	0.62
Supraventricular tachycardia	TTN	3,059	1.35 [1.08, 1.70]	0.01
Mitral valve disease	TTN	3,059	1.45 [1.18, 1.78]	8.26 x 10−4
Quantitative traits
Trait	Gene	Carriers	Effect in s.d. [95% CI]	P-value
Height, cm	SCUBE3	153	−0.67 [−0.95, −0.39]	3.90 x 10−6
	PIEZO1	577	−0.35 [−0.50, −0.21]	1.97 x 10−6
	IRS1	36	−0.67 [−1.24, −0.11]	0.02
	ANGPTL2	78	−1.02 [−1.41, −0.64]	2.45 x 10−7
	PAPPA	69	−0.47 [−0.89, −0.05]	0.03
	ZFAT	42	0.79 [0.24, 1.34]	5.04 x 10−3
	DTL	45	−0.90 [−1.41, −0.39]	5.69 x 10−4
Glucose	GIGYF1	102	0.55 [0.37, 0.73]	1.37 x 10−9
HDL	NR1H3	122	0.38 [0.22, 0.54]	2.97 x 10−6
	PLIN1 *	97	0.36 [0.18, 0.54]	9.29 x 10−5
LDL	GIGYF1	105	−0.29 [−0.47, −0.11]	1.76 x 10−3

P-values, odds ratios (OR) and 95% confidence intervals (95% CI) were obtained from whole-genome ridge-regression models implemented in REGENIE, further adjusting for sex, age and associated principal components (PCs). P-values shown are unadjusted for multiple testing. Novel indicates that rare variant associations were not reported prior to the release of UK Biobank exomes. Association test between Igf-1 and JAK2 was not performed due to low cumulative minor allele counts (cMAC); cMAC among individuals with Igf-1 was 2.

^*The association between PLIN1 and HDL was added to replication because the direction of effect (increased HDL) was different to the direction reported in family-based studies of partial lipodystrophy.