. 2023 Nov 2;14:1235337. doi: 10.3389/fgene.2023.1235337

Copyright © 2023 de las Fuentes, Schwander, Brown, Bentley, Winkler, Sung, Munroe, Miller, Aschard, Aslibekyan, Bartz, Bielak, Chai, Cheng, Dorajoo, Feitosa, Guo, Hartwig, Horimoto, Kolčić, Lim, Liu, Manning, Marten, Musani, Noordam, Padmanabhan, Rankinen, Richard, Ridker, Smith, Vojinovic, Zonderman, Alver, Boissel, Christensen, Freedman, Gao, Giulianini, Harris, He, Hsu, Kühnel, Laguzzi, Li, Lyytikäinen, Nolte, Poveda, Rauramaa, Riaz, Robino, Sofer, Takeuchi, Tayo, van der Most, Verweij, Ware, Weiss, Wen, Yanek, Zhan, Amin, Arking, Ballantyne, Boerwinkle, Brody, Broeckel, Campbell, Canouil, Chai, Ida Chen, Chen, Chitrala, Concas, de Faire, de Mutsert, de Silva, de Vries, Do, Faul, Fisher, Floyd, Forrester, Friedlander, Girotto, Gu, Hallmans, Heikkinen, Heng, Homuth, Hunt, Ikram, Jacobs, Kavousi, Khor, Kilpeläinen, Koh, Komulainen, Langefeld, Liang, Liu, Liu, Lohman, Mägi, Manichaikul, McKenzie, Meitinger, Milaneschi, Nauck, Nelson, O’Connell, Palmer, Pereira, Perls, Peters, Polašek, Raitakari, Rice, Rice, Rich, Sabanayagam, Schreiner, Shu, Sidney, Sims, Smith, Starr, Strauch, Tai, Taylor, Tsai, Uitterlinden, van Heemst, Waldenberger, Wang, Wei, Wilson, Xuan, Yao, Yu, Yuan, Zhao, Becker, Bonnefond, Bowden, Cooper, Deary, Divers, Esko, Franks, Froguel, Gieger, Jonas, Kato, Lakka, Leander, Lehtimäki, Magnusson, North, Ntalla, Penninx, Samani, Snieder, Spedicati, van der Harst, Völzke, Wagenknecht, Weir, Wojczynski, Wu, Zheng, Zhu, Bouchard, Chasman, Evans, Fox, Gudnason, Hayward, Horta, Kardia, Krieger, Mook-Kanamori, Peyser, Province, Psaty, Rudan, Sim, Smith, van Dam, van Duijn, Wong, Arnett, Rao, Gauderman, Liu, Morrison, Rotter and Fornage.

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TABLE 1.

Summary of novel loci.

Locus	rsID ^a	Chr	Pos (hg19)	Coded allele	Coded allele Freq ^b	Beta₀ ^c	Beta₁ ^d	2 DF P ^e	1 DF G × E P ^f	N	Genes ^g	RefPop-trait-Exp ^h
1	rs139845754	1	180,258 167	A	0.052	−0.101	−0.06	3.40E-08	2.00E-01	10,913	LHX4; RP5-11 80C10.2; *ACBD6* ; XPR1; KIAA1614; STX6	AFR-TG-SomeCol
2 ⁱ	rs7567133	2	103,239 356	C	0.031	0.102	0.021	1.72E-08	1.16E-03	6,361	IL1RL1; IL18R1; IL18RAP; SLC9A4; *SLC9A2;* MFSD9; TMEM182	AFR-HDL-GradCol
3	rs79367750	3	9,096 107	C	0.096	1.251	−10.279	3.99E-08	1.94E-04	8,855	*SRGAP3*	EAS-LDL-SomeCol
4 ⁱ	rs147731578	3	70,605 665	ATTATT	0.018	−0.145	0.034	1.39E-09	3.51E-09	15,584	MITF; FOXP1	EUR-HDL-SomeCol
5 ⁱ	rs74620279	4	179,620 483	C	0.025	−12.24	11.59	4.67E-08	1.39E-06	5,669	SNORD65	AFR-LDL-SomeCol
6	rs77249395	4	181,181 245	G	0.035	0.006	−0.026	3.17E-06	2.41E-08	134,413	LINC00290	TA-HDL-GradCol EUR-HDL-GradCol
7 ⁱ	rs11132093	4	182,664 815	A	0.061	−1.65	15.84	5.04E-09	4.10E-07	2,809	RP11-540E16.2; TENM3	EAS-LDL-GradCol
8	rs190502162	5	37,160 808	C	0.013	9.266	−0.715	3.35E-08	4.04E-07	48,467	SKP2; NADK2; RANBP3L; SLC1A3; NIPBL; *CPLANE1* ; NUP155; WDR70; GNDF	EUR-LDL-SomeCol
9	rs192718305	5	82,514 005	G	0.025	3.481	19.901	2.05E-08	1.60E-03	5,664	RP11-343L5.2; TMEM167A; *XRCC4*	AFR-LDL-SomeCol
10 ⁱ	rs147892694	6	76,693 587	G	0.034	−0.037	−0.087	8.61E-09	1.20E-01	8,599	TMEM30A; FILIP1; SENP6; MYO6; *IMPG1*	AFR-HDL-SomeCol
11	rs7015	7	97,920 623	A	0.203	−1.142	−0.526	4.56E-08	6.18E-02	157,929	LMTK2; TECPR1; *BRI3* ; BAIAP2L1; NPTX2	CPA-LDL-SomeCol
12 ^j	rs77655002	8	30,437 023	C	0.042	−9.97	10.73	5.52E-09	7.65E-08	7,166	MBOAT4; RBPMS-AS1; RBPMS; *GTF2E2* ; GSR; TEX15	AFR-LDL-GradCol CPA-LDL-GradCol
13	rs144190766	10	108,927 076	C	0.03	−0.015	−0.103	2.52E-08	5.64E-03	9,677	SORCS1; RNA5SP326	AFR-HDL-SomeCol
14	rs116562538	10	129,845 329	A	0.028	−4.573	−9.049	6.79E-09	4.82E-02	20,939	*PTPRE*	CPA-LDL-SomeCol
15	rs35287906	11	4,041 010	C	0.014	3.405	−5.247	1.53E-09	7.71E-11	81,020	PGAP2; RHOG; *STIM1* ; RRM1; OR55B1P; RP11-23F23.3	EUR-LDL-GradCol
16	rs11230661	11	55,451 313	A	0.185	0.01	0.007	3.15E-10	3.90E-01	151,320	TRIM48; TRIM51; 87 Olfactory Receptor Genes; APLNR	EUR-HDL-GradCol EUR-HDL-SomeCol
17 ⁱ	rs148063115	12	14,221 135	T	0.026	0.022	0.222	4.86E-08	4.35E-03	6,168	GRIN2B; RP11-72J9.1; RP11-298E10.1; RN7SL676P; GUCY2C	AFR-TG-GradCol
18 ⁱ	rs190746034	13	101,418 063	G	0.022	−0.002	−0.158	1.26E-08	1.06E-05	6,361	RP11-151A6.4; TMTC4; *NALCN-AS1* ; ARF4P3	AFR-HDL-GradCol

Notes:

^{^a}

rsID, based on dbSNP, build 146.

^{^b}

Coded allele frequency.

^{^c}

Effect size (beta) of the unexposed group.

^{^d}

Effect size (beta) of the exposed group.

^{^e}

GWAS, 2 DF p-value of the significant lead SNP, for this locus.

^{^f}

GWAS, 1 DF, genetic-educational attainment interaction p-value of the significant lead SNP, for this locus.

^{^g}

Nearest gene of all SNVs, in LD (r2>0.2) with lead variant; if SNV, not in FUMA, gene or nearest flanking coding genes noted. Bolded genes reflect intragenic lead SNV.

^{^h}

The reference panel used in FUMA, to obtain functional annotations-trait-exposure; if more than one RefPop-Trait-Exp listed, the data provided is for the more significant association which is listed first.

^ⁱ

Only significant in Stage I analyses.

^{^j}

2DF p = 1.83E-08, 1 DF G×E p = 4.14E-08 in CPA-LDL-GradCol analyses.

AFR, african population; EAS, east asian population; EUR, european population; GradCol, graduated college; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; CPA, cross-population analyses; TG, triglyceride.