Effect of SPTLC1 on type 2 diabetes mellitus

Table 1 The clinical features of proband and family members

Features	Normal range	III-1 (proband)	IV-1	II-2
Gender		Male	Male	Female
Age at admission, years		44.00	19.00	68.00
Age at DM onset, years		42.00	17.00	53.00
Weight, kg		50.00	70.00	51.00
Height, cm		170.00	174.00	156.00
Waist, cm		71.00	82.00	87.00
BMI, kg/m2		17.30	23.12	20.96
SBP, mmHg		118.00	130.00	129.00
DBP, mmHg		90.00	85.00	68.00
FCP, ng/mL	0.81-1.89	1.04		1.16
2hCP, ng/mL		2.39		1.30
FINS, μU/L	4.00-12.00		12.65
2hINS, μU/L			83.15
HbA1c, %	3.60-6.00	12.6	10.80	10.40
TC, mmol/L	3.10-5.20	3.90	3.29	4.95
TG, mmol/L	0.56-1.70	0.95	1.01	0.93
HDL, mmol/L	1.00-1.55	1.06	0.89	1.21
LDL, mmol/L	1.90-3.10	2.45	1.84	3.03
Hs-CRP, mg/L	0.00-3.00	0.37	1.57	5.16
GADA	Negative	Negative	Negative
IAA	Negative	Negative	Negative
IA-2A	Negative	Negative	Negative
ICA	Negative	Negative	Negative
ACR, mg/g	0.00-30.00	16.85		25.66
Ketobodies in urine	Negative	Negative	Negative	Negative
DR	Negative	No	No	No

ACR: Albumin to creatinine ratio; BMI: Body mass index; CRP: C-reactive protein; DBP: Diastolic blood pressure; DM: Diabetes mellitus; DR: Diabetic retinopathy; FCP: Fasting C-peptide; FINS: Fasting insulin; GADA: Glutamic acid decarboxylase autoantibody; HbA1c: Hemoglobin A1c; HDL: High-density lipoprotein cholesterol; IA-2A: Protein tyrosine phosphatase autoantibody; IAA: Autoantibody against to insulin; ICA: Islet cell autoantibody; LDL: Low-density lipoprotein cholesterol; SBP: Systolic blood pressure; TC: Total cholesterol; TG: Triglyceride; 2hCP: 2-hour postprandial C-peptide; 2hINS: 2-hour postprandial insulin.

Table 2 The rare variant gene-level association between SPTLC1 and type 2 diabetes mellitus

Mask	Methods	Sample size	Combined allele frequency (%)	Passing variants	Singleton variants	SD	Odds ratio	P value
LofTee	Predicted loss of function	43125	0.03942	14	11	0.52284	2.1014	0.13368
16/16	Predicted deleterious by 16 methods	43125	0.04638	15	11	0.47401	1.8749	0.16848
11/11	Predicted deleterious by 11 methods	43125	0.09507	29	20	0.33683	2.0718	0.025839
5/5	Predicted deleterious by 5 methods	43125	0.15072	31	21	0.2571	1.3852	0.20087
5/5 + LofTee LC	Predicted deleterious by 5 methods, plus LofTee low confidence	43125	0.16464	33	21	0.24528	1.3551	0.21151
5/5 + 1/5, 1%	Predicted deleterious by 5 methods, plus variants with MAF < 1% that are predicted to be deleterious by 1 of 5 methods	43125	0.85565	95	59	0.10614	1.0444	0.68172
5/5 + 0/5, 1%	Predicted deleterious by 5 methods, plus variants with MAF < 1% that are not predicted to be deleterious by any of 5 methods	43125	0.92058	102	63	0.10226	1.0154	0.88112
Total		43125					2.4968	0.0164

LC: Low confidence; LofTee: Loss-of-function transcript effect estimator; MAF: Minor allele frequency.