[Preprint]. 2023 Mar 31:2023.03.31.23287839. [Version 1] doi: 10.1101/2023.03.31.23287839

Table 1.

Cardiometabolic profile, exemplar loci, and physiological impact of index SNVs at T2D association signals allocated to eight mechanistic clusters.

Mechanistic cluster	Cardiometabolic profile	Number of T2D associations	Exemplar loci	Physiological impact
Mechanistic cluster	Cardiometabolic profile	Number of T2D associations	Exemplar loci	Insulin secretion	Insulin sensitivity
Beta-cell +PI	+FG^, +2hG^, +HbAlc, +PI^*	91	TCF7L2, KCNQ1, CDKAL1, CDKN2A-CDKN2B, SLC30A8	−	+
Beta-cell −PI	+FG^, +2hG^, +HbAlc, −PI^*	89	CDC123-CAMK1D, HNFIB, KCNJ11-ABCC8, HNF4A, HNFIA	−	+
Residual glycaemic	+FG^*, +HbAlc	389	GCC1-PAX4-LEP, ANKRD55, GCKR, UBE2E2	−	−
Body fat	+body fat, +ASAT^*	273	ZMIZ1, HMGA2, CTBP1	+	−
Metabolic syndrome	+FG^, +FI^, +WHR, +VAT^, −GFAT^, +TG, −HDL, +BP	166	IGF2BP2, CCND2, HHEX- IDE, JAZF1, GPSM1	+	−
Obesity	+BMI, +WHR, +body fat, +BMR, +TG, −HDL	233	FTO, MC4R, MACF1, TMEM18	+	−
Lipodystrophy	+FI^, +WHR, −body fat, −GFAT^, +TG, −HDL, +BP	45	IRS1, GRB14-COBBL1, PPARG	+	−
Liver/lipid metabolism	−LDL, −TC, +liver fat, +liver biomarkers	3	TOMM40-APOE-GIPR, TM6SF2, PNPLA3	−	−

+/−: T2D risk alleles associated with increased/decreased phenotype values.

FG: fasting glucose. FI: fasting insulin. 2hG: two-hour glucose. HbA1c: glycated haemoglobin. PI: proinsulin. BMI: body mass index. WHR: waist-hip ratio. VAT: visceral adipose tissue volume. ASAT: abdominal subcutaneous adipose tissue volume. GFAT: gluteofemoral adipose tissue volume. LDL: low-density lipoprotein cholesterol. HDL: high-density lipoprotein cholesterol. TC: total cholesterol. TG: triglycerides. BMR: basal metabolic rate. BP: blood pressure.

adjusted for BMI.