Whole-exome sequencing identifies novel protein-altering variants associated with serum apolipoprotein and lipid concentrations

Table 4 Replication of the gene-level associations in the lipid WES by Hindy et al. [13], and in the UK Biobank WES [32] (associations with p<0.05)

		Total CHOL		HDL		LDL		TG		TG-to-HDL		apoA		apoB
GENE	Test	P	beta	P	beta	P	beta	P	beta	P	beta	P	beta	P	beta
LIPC	Burden	0.0012	2.86	1.6×10⁻²⁵	2.62	0.046	−1.59	2.5×10⁻⁷	0.05
LIPC	SKAT			3.4×10⁻²⁰	2.62	0.0015	−1.59	0.014	0.05
LIPC	UK M1	5.5×10⁻⁴	0.13	9.0×10⁻³²	0.41			5.3×10⁻⁴	0.13			1.4×10⁻³⁵	0.45
LIPC	UK M3	3.4×10⁻¹⁵	0.12	7.7×10⁻⁹⁵	0.29			1.6×10⁻¹⁸	0.13			4.9×10⁻¹¹⁰	0.33	0.038	0.03
RBM47	Burden							0.0013	−0.04	0.0028	−0.05
RBM47	SKAT							0.0058	−0.04	0.0071	−0.05
RBM47	UK M1	0.045	0.24			0.0027	0.37							7.8×10⁻⁴	0.41
CYP3A43	Burden							0.019	0.02	0.019	0.03
CYP3A43	SKAT							0.0056	0.02	0.013	0.03
GTF3C5	UK M1	0.027	−0.12			0.029	−0.12							0.042	−0.11
AKAP3	UK M1											0.032	−0.10
RYR3	UK M3			0.036	−0.02

Burden and SKAT burden/SKAT test in lipid WES by Hindy et al. [13], for PAVs predicted to be deleterious; UK M1/M3 UK Biobank gene aggregate test for putative loss-of-function variants/deleterious PAVs of 1% [32]. Associations significant after correction for 12 genes are highlighted with bold type. No associations were significant for non-HDLC

ISSN: 1756-994X