The Genetic Analysis Workshop 16 Problem 3: simulation of heritable longitudinal cardiovascular phenotypes based on actual genome-wide single-nucleotide polymorphisms in the Framingham Heart Study

Table 2 Summary characteristics of the major genes and polygenes for traits HDL, LDL, and TG^a

No.	Trait	Chr	Symbol^b	Gene	SNP	Role	Total	h ²	Model^c	MAF	h² of polygenes
1	HDL	9q31.1	α ₁	ABCA1	rs10820738	Intron/Exon boundary		0.010	DOM	6.7
2	HDL	19q13.2	α ₂	CYP2B7P1	rs8103444	Exon/Intron boundary		0.002	ADD	24.4
3	HDL	15q21	α ₃	LIPC	rs8035006	Intron		0.003	ADD	32.5
4	HDL	8p22	α ₄	LPL	rs3200218	Exon downstream		0.003	DOM	21.7
5	HDL	19q13.2	δ ₁	CYP2B6	rs8192719	Exon/Intron boundary (Rx)		0.003	ADD (up 10%)^d	24.9
							Total	0.021
6	HDL	1,000 SNPs	[apoly]					0.58	ADD	≠	min = 0.0003; max = 0.0015; avg = 0.00058
							Total	0.60
1	LDL	4p16.3	β ₁	LRPAP1	rs7672287	Intron		0.003	ADD	22.2
2	LDL	12q13	β ₂	LRP1	rs1466535	Intron		0.002	ADD	31.6
3	LDL	11q13.4	β ₃	LRP5	rs901824	Intron/Exon boundary		0.001	ADD	10.3
4	LDL	chrom1	β ₄		rs10910457			0.005	ADD	1.0
5	LDL	8p22 × 4q24	β ₅	LPL × NFKB1	rs4648068	Intron		0.007	INT	31.0
6	LDL	22q12.2	δ ₂	SLC5A4	rs2294207	Intron	(Rx)	0.010	ADD (down 30%)	25.7
							Total	0.028
7	LDL	1,000 SNPs	[bpoly]					0.52	ADD	≠	min = 0.0003; max = 0.00128; avg = 0.00052
							Total	0.55
1	TG	11q23	γ ₁	APOA5	rs603446	Downstream		0.003	OVERD	43.3
2	TG	8p22	α ₄	LPL	rs3200218	Exon downstream		0.004	ADD	21.7
3	TG	19q13.2	δ ₁	CYP2B6	rs8192719	Exon/Intron boundary (Rx)		0.003	ADD (down 15%)	24.9
4	TG		diet					0.01	Familial
							Total	0.020
5	TG	1,000 SNPs	[gpoly]					0.38	ADD	≠	min = 0.0002; max = 0.0009; avg = 0.00038
							Total	0.40

^aAbbreviations: MAF, Minor allele frequency; min, minimum; max, maximum; avg, average; h², heritability; [apoly], a vector of 1,000 polygenes that contribute to HDL; [bpoly], a vector of 1,000 polygenes that contribute to LDL; [gpoly], a vector of 1,000 polygenes that contribute to TG.
^bSymbol represents a locus/a vector of polygenes marked by SNPs and corresponding genes, which can be introns/exons, or a diet effect.
^cEffects of genes were simulated based on ADDitive (0, 0.5, 1), DOMinant (1, 1, 0), OVERDominant (0, 1, 0), and INTeraction genetic models.
^dMedication treatment lowered LDL on a varying percentage of participants dependent on visits: 2% of subjects in Visit 1, 5% of subjects in Visit 2, and 15% of subjects in Visit 3. Medication treatment increased HDL 10%, lowered LDL 30%, and lowered TG 15% for the treated subjects and in accordance with specific types of genotypes, shown in the "Model" column. For HDL on chromosome 11, 39 SNPs were simulated as a block of polygenes, starting at 110 Mbp and ending at 134 Mbp, with approximately an average equidistance of 0.5 Mbp.

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