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

Table 1 Single-variant association results for variants reaching exome-wide significance (p<4.3×10⁻⁷), or with evidence of replication in type 1 diabetes (p<0.05) or in the general population (p<0.05/27/8=2.3×10⁻⁴)

Gene	Variant	MAF	SIFT/PolyPhen	Phenotype	N	P-value	Beta (se)	P_Repl	P lipids
LIPC	15:58563549 C>T p.Thr405Met rs113298164	0.017	Deleterious, probably damaging	apoA1	918	7.8×10⁻⁸	0.98 (0.18)	0.89	apoA (UKBB): p=9.3×10⁻⁴⁶
GTF3C5	9:133054787 C>T p.Ala382Val rs202207045	0.007^b	Tolerated, benign	LDLC	894	1.3×10⁻⁶	−1.35 (0.28)	0.02	LDLC (Hindy): p=0.125
GTF3C5	9:133054787 C>T p.Ala382Val rs202207045	0.007^b	Tolerated, benign	Non-HDLC	919	7.3×10⁻⁷	−1.38 (0.28)	0.02	Non-HDLC (Hindy) p=0.199
FNDC3A	13:49201861 A>G p.Thr1017Ala rs45604939	0.064	Deleterious, probably damaging	CHOL^a	748	8.8×10⁻⁶	0.46 (0.10)	0.04	CHOL (Hindy) p=0.35
PPIC	5:123023945 T>C p.Asn190Ser rs451195	0.156	Deletorious, benign	HDLFC L	487	5.0×10⁻⁶	0.43 (0.09)	0.87	HDLC (GLGC) p=2.1×10⁻⁷
ZNF274	19:58206912 A>G p.Gln118Arg rs45580533	0.021	Tolerated, benign	VLDL L	487	9.3 ×10⁻⁶	−1.02 (0.23)	0.87	LDL (GLGC) p=3.0×10⁻¹³
ZNF274	19:58206912 A>G p.Gln118Arg rs45580533	0.021	Tolerated, benign	VLDLTG L	748	5.5 ×10⁻⁶	−10.5 (0.23)	0.81	TG (GLGC) p=0.003

Variant chromosome:base pair position with REF>ALT alleles, amino acid change, and rs identifier, MAF minor allele frequency, SIFT/Polyphen predicted effect, Beta (se) effect size beta and standard error, P_ReplP-value for replication in GWAS data, P lipids the lowest p-value within the GLGC GWAS, UKBB WES, and lipid WES (Hindy et al.) for the corresponding or closest matching lipid phenotype
^ars45604939 association with total cholesterol was obtained for the NMR measured total cholesterol; replication with standard laboratory total cholesterol
^brs202207045 MAF in Hindy et al. was markedly lower, 2.5×10⁻⁵

ISSN: 1756-994X