Identification and MS-assisted interpretation of genetically influenced NMR signals in human plasma

Table 1 Genetic associations with NMR intensities and ratios between NMR intensities.

Locus	SNP	CHR^a	POS^a	A^a	B^a	MAF	Chemical shift(ppm)	n	Beta'^b	P value	Chemical shifts for ratios (ppm)	n	Beta' ratios^b	P value ratios	P gain^c
GCKR	rs780094	2	27,594,741	T	C	41.4%	1.370	1,688	0.0413	1.2x10^-10	3.286/1.370	1,667	-0.0407	2.8x10^-15	4.3x10⁴
CPS1	rs2216405	2	211,325,139	C	T	19.3%	3.599	1,719	0.0456	4.5x10^-14	3.599/2.475	1,718	0.0459	1.8x10^-19	2.5x10⁵
PYROXD2	rs4488133	10	100,149,126	A	T	34.3%	2.757	1,735	-0.0190	7.3x10^-12	2.757/2.755	1,734	-0.0123	2.9x10^-94	2.5x10⁸²
FADS1	rs174547	11	61,327,359	C	T	30.0%	2.801	1,733	-0.0408	4.0x10^-35	2.801/2.017	1,724	-0.0449	1.1x10^-94	3.8x10⁵⁹
APOA1	rs3741298	11	116,162,771	C	T	21.4%	2.038	1,724	0.0363	8.4x10^-11	4.162/4.082	1,715	-0.0138	1.8x10^-14	4.6x10³
LIPC	rs4775041	15	56,461,987	C	G	28.5%	1.283	1,671	0.0320	1.4x10^-10	1.068/1.029	1,664	-0.0056	3.6x10^-21	4.0x10¹⁰
CETP	rs247617	16	55,548,217	A	C	31.3%	3.259	1,705	0.0529	7.6x10^-15	2.211/2.011	1,695	-0.0124	1.1x10^-18	6.8x10³

The locus name indicates the gene that most likely hosts the causative SNP.
A/B: minor/major allele; MAF: minor allele frequency; n: number of samples where genetic and NMR data are jointly available; ppm: parts per million.
^aChromosomal location (CHR, POS), minor (effect, A) and major (B) alleles are reported with respect to the positive strand of the human genome (NCBI build 36.1).
^bBeta': relative effect size, defined as beta' = (10^beta- 1), where beta is the slope in the linear model (using log₁₀-scaled traits) and genotype is coded as 0-1-2 (major-hetero-minor genotype). Beta' represents the relative difference per copy of the minor allele for the unscaled metabolic trait (NMR bin or NMR ratio) compared to the estimated mean of the major allele homozygote group (intercept of the linear model).
^cThe P gain is defined as min(p(S₁)/p(S₁/S₂), p(S₂)/p(S₁/S₂)), where p(S₁), p(S₂), and p(S₁/S₂) denote the P values of association of two log-scaled NMR intensities at chemical shift S₁ and S₂, and of their ratio S₁/S₂, respectively.

ISSN: 1756-994X