Genotype-based recall to study metabolic effects of genetic variation: a pilot study of PPARG Pro12Ala carriers

Figures & data

Figure 1. Schematic flow chart describing the study design.

Table 1. Protein-altering variants in the EpiHealth cohort with ≥10 participants homozygous for minor alleles^a.

rsID	Chromosome	Position (b37)	Minor/Major allele	N (aa)	N (aA)	Locus
rs1137101	1	66058513	A/G	531	1,090	LEPR
rs1935	10	64927823	G/C	528	1,113	JMJD1C
rs492594	2	169764176	C/G	474	1,038	G6PC2
rs13928	7	44153780	G/A	451	1,112	AEBP1
rs3784634	15	62259637	C/T	445	1,055	VPS13C
rs10851704	15	62202482	C/T	421	1,064	VPS13C
rs1208	8	18258316	G/A	377	1,074	NAT2
rs5215	11	17408630	C/T	367	1,034	KCNJ11
rs5219	11	17409572	T/C	366	1,035	KCNJ11
rs12529	10	5136651	G/C	303	1,014	AKR1C3
rs9938550	16	30999142	A/G	276	1,021	HSD3B7
rs1260326	2	27730940	T/C	261	980	GCKR
rs11057401	12	124427306	A/T	240	981	CCDC92
rs13266634	8	118184783	T/C	221	937	SLC30A8
rs1169288	12	121416650	C/A	216	1011	HNF1A
rs9814557	3	135720540	G/A	215	964	PPP2R3A
rs17197552	3	135722264	G/A	215	965	PPP2R3A
rs56200889	11	72408055	C/G	197	890	ARAP1
rs61748245	2	165476253	A/T	179	876	GRB14
rs2464196	12	121435427	A/G	177	935	HNF1A
rs1799930	8	18258103	A/G	172	931	NAT2
rs1137100	1	66036441	G/A	171	952	LEPR
rs6779903	3	135720851	T/G	153	847	PPP2R3A
rs321776	5	55407542	T/C	151	861	ANKRD55
rs17570	19	33878837	A/G	141	847	PEPD
rs1800437	19	46181392	C/G	104	779	GIPR
rs10761725	10	64974537	A/T	84	716	JMJD1C
rs17244632	2	165551404	A/G	75	670	COBLL1
rs17185413	11	61730553	C/T	71	675	BEST1
rs479661	2	169721377	G/A	65	590	NOSTRIN
rs7657817	4	89668859	T/C	60	615	FAM13A
rs9898682	17	41738823	A/G	52	445	MEOX1
rs12453522	17	41931375	G/A	49	555	CD300LG
rs10445686	2	135893372	G/A	45	477	RAB3GAP1
rs7607980	2	165551201	C/T	40	490	COBLL1
rs12440118	15	42744094	G/A	39	513	ZFP106
rs8940	7	116146074	G/C	35	514	CAV2
rs1801282	3	12393125	G/C	31	561	PPARG
rs7130656	11	45832509	G/A	30	477	SLC35C1
rs12702	15	44093927	C/T	24	315	C15orf63
rs328	8	19819724	G/C	17	372	LPL
rs12907567	15	62214607	T/C	13	284	VPS13C
rs11629598	15	62243197	C/T	13	284	VPS13C
rs2303405	15	62253791	C/T	13	281	VPS13C
rs10488698	11	116633947	A/G	13	285	BUD13
rs74459242	2	165578602	T/C	10	252	COBLL1

List of protein-altering variants annotated in the NHLBI Exome Sequencing Project.

^a The genotype counts refers to unrelated individuals of European descent for which the association tests were performed.

Table 2. Baseline characteristics of participants in the GBR study as genotyped by their carrier status of PPARG Pro12Ala^a.

	GBR study
Phenotype	Pro/Pro (n = 12)	Pro/Ala (n = 15)	Ala/Ala (n = 13)	p value
Age	64 (9)	63 (9)	64 (8)	0.92
Women (%)	8 (67)	9 (60)	9 (69)	0.92
BMI (kg/m^2)	26.8 (3.3)	24.3 (3.2)	26.6 (3.6)	0.71
Waist–hip ratio	0.91 (0.06)	0.89 (0.08)	0.92 (0.07)	0.85
Fat percentage (%)	32.3 (8.8)	30.5 (6.6)	32.9 (7.1)	0.66
Fasting glucose (mmol/L)	5.88 (0.48)	5.83 (0.52)	5.89 (0.52)	0.57
Total cholesterol (mmol/L)	5.41 (0.60)	5.63 (0.80)	6.05 (0.90)	0.13
HDL cholesterol (mmol/L)	1.51 (0.34)	1.49 (0.31)	1.59 (0.27)	0.42
LDL cholesterol (mmol/L)	3.40 (0.54)	3.48 (0.65)	3.85 (0.93)	0.23
Triglycerides (mmol/L)	0.86 (0.27)	1.07 (0.48)	1.20 (0.48)	0.12

^aThe numbers given are either counts, percentages, or mean (standard deviation). The reported p values of the association between the phenotype and copies of the minor allele come from linear regressions adjusted for age, sex, and ancestry components under an additive model. The p value for age and sex comes from an ANOVA and a Fisher’s exact test, respectively. The beta from the regression is not shown. Use of medication is self-reported.

HDL: high-density lipoprotein; LDL: low-density lipoprotein. There was a varying number of missing observations for different phenotypes.

Table 3. Metabolic variables of participants in the GBR study as genotyped by their carrier status of PPARG Pro12Ala^a.

Phenotype	Pro/Pro (n = 12)	Pro/Ala (n = 15)	Ala/Ala (n = 13)	p value
Fasting insulin (mU/L)	6.85 (4.06)	7.13 (3.36)	7.42 (3.20)	0.94
C-peptide (nmol/L)	0.68 (0.21)	0.70 (0.25)	0.67 (0.19)	0.33
HbA1c, IFCC (mmol/mol)	35.3 (3.0)	34.7 (3.2)	35.0 (3.6)	0.95
HOMA-IR	1.85 (1.33)	1.88 (0.98)	1.98 (0.98)	0.88
2h glucose (mmol/L)	8.61 (2.16)	7.63 (2.05)	8.95 (1.91)	0.75
Glucose, OGTT AUC180 min × mmol/L	1,503 (263)	1,335 (261)	1,493 (276)	0.82
Insulin, OGTT AUC180 min × mU/L	9,914 (7,311)	6,622 (3,269)	8,337 (5,680)	0.25
Matsuda index	5.35 (1.97)	6.66 (3.49)	5.64 (1.87)	0.43
Revised QUICKI	0.20 (0.01)	0.20 (0.01)	0.19 (0.01)	0.78
NEFA, OGTT AUC120 min × µmol/L	13,629.5 (7,073.83)	11,036.74 (3,810.39)	13,942.60 (5,467.38)	0.96
NEFA at baseline (µM)	206 (67)	218 (78)	243 (93)	0.57
Glycerol, OGTT AUC120 min × µmol/L	7,210.81 (2,967.45)	6,086.46 (2,977.29)	7,116.01 (2,967.64)	0.91
Glycerol at baseline (µM)	83.1 (28.7)	84.71 (46.0)	82.3 (33.6)	0.99

^a The numbers given are either counts (percentages) or means (standard deviations). p values represent associations between number of minor alleles and phenotype under an additive model from linear regressions adjusted for age, sex, and ancestry components.

AUC: area under the curve; HOMA-IR: homeostatic model assessment of insulin resistance.