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Frontiers of Engineering Management

ISSN 2095-7513

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Front. Eng    2016, Vol. 3 Issue (1) : 30-38    https://doi.org/10.15302/J-FEM-2016008
Engineering Management Treatises
Genetic Study Identifies CBLN4 as a Novel Susceptibility Gene for Accident Proneness
Shu-lin Zhang1,Hui-qing Jin1,*(),Yang Song2,Wan-sheng Yu1,Liang-dan Sun3
1. Anhui Sanlian University, Hefei 230601, China; National Center of Engineering and Technology for Vehicle Driving Safety, Hefei 230081, China
2. National Center of Engineering and Technology for Vehicle Driving Safety, Hefei 230081, China; Shanghai Zhuke Academy of Information Technology, Shanghai 201203, China
3. Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei 230032, China
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Abstract

Frequent traffic accidents constitute a major danger to human beings. The accident-prone driver who has the stable physiological, psychological, and behavioral characteristics is one of the most prominent causes of traffic accidents. The internal link between the individual characteristics and the accident proneness has been a difficult point in the accident prevention research. The authors selected accident-prone drivers as cases and safe drivers as controls (case-control group) from 18,360 drivers who were enrolled from three public transportation incorporations of China using area stratified sampling method. The case-control groups were 1:1 matched. The authors performed genome-wide association study (GWAS) by 179 cases and 179 controls using the U.S. Affymetrix Genome-Wide Human Mapping SNP 6.0 Array. The authors observed that the gene frequencies of 34 single-nucleotide polymorphisms (SNPs) in three regions of cases were higher than those in the control (P<10−4). The authors then tested two independent replication sets for strong association 6 SNPs in 349 pairs of case-control drivers using the U.S. ABI 3730 sequencing method. The results indicated that SNP rs6069499 within linked CBLN4 gene are strongly associated with accident proneness (Pcombined=6.37×10−10). According to CBLN4 gene mainly involved in adrenal development and the regulation of secretion, the authors performed 12 biochemical parameters of the blood using radioimmunoassay. The levels of dopamine (DA) and adrenocorticotropic (ACTH) hormone showed significant differences between accident-prone drivers and safe drivers (PDA=0.03, PACTH=0.01). It is suggested that the accident-prone drivers may have the idiosyncrasy of susceptibility.
Keywords accident proneness      genome-wide association study (GWAS)      dopamine (DA)      ACTH      susceptibility gene      traffic accident epidemiology      accident prevention      traffic safety      three-dimensional model     
Corresponding Author(s): Hui-qing Jin   
Online First Date: 05 May 2016    Issue Date: 26 May 2016
 Cite this article:   
Shu-lin Zhang,Hui-qing Jin,Yang Song, et al. Genetic Study Identifies CBLN4 as a Novel Susceptibility Gene for Accident Proneness[J]. Front. Eng, 2016, 3(1): 30-38.
 URL:  
https://academic.hep.com.cn/fem/EN/10.15302/J-FEM-2016008
https://academic.hep.com.cn/fem/EN/Y2016/V3/I1/30
Index Unit Abnormal Normal
Speed anticipation ms <800 or>2500 800?2500
Discrimination reaction judgment (error reaction) time >5 ≤5
Attention distribution and duration (error action) time >110 ≤110
Depth perception mm <?22 or>22 ±22
Dynamic vision <0.2 ≥0.2
Night vision s >35 ≤35
Tab.1  Diagnostic Test Standards for the Candidates of Cases and Controls (From Chinese National Standard GB18463-2001)
Case group Matching-control group
Age Similar (difference less than 2 years old)
Gender Same
Nationality Same
Residence Same
Education Same
Driving duration Similar (difference less than 2 years)
Driving training Same (the same driving training school)
Driving route Same (such as bus No. 2)
Marital status Same
Tab.2  Matching Conditions of the Case Drivers and Control Drivers
Fig.1  PCA plot of 1056 participants from 3 samples (528 cases and 528 controls). The orange points are cases, and the blue points are controls. (a) PCA plot of the GWAS and replication 1 samples; (b) PCA plot of the GWAS and replication 2 samples.
dbSNP RS ID Chr PhysicalPosition AlleleA/B Association gene P OR OR (95%CL)
rs2033581 8 69264902 A/G DEPDC2 2.10×10-6 0.4629 0.3365?0.6368
rs6978138 7 16856893 A/G AGR2 4.70×10-5 0.5443 0.4011?0.7385
rs1019621 7 135000000 A/G CNOT4///STRA8 1.12×10-5 0.4485 0.3047?0.6603
rs292661 7 135000000 C/T CNOT4///STRA8 9.01×10-5 0.4972 0.3317?0.7452
rs2972106 7 148000000 C/T CNTNAP2 9.31×10-5 0.5272 0.3748?0.7414
rs2717741 8 18490786 C/G PSD3 1.80×10-5 3.2696 1.7794?6.0078
rs2634449 8 18488730 A/G PSD3 1.80×10-5 0.2772 0.1489?0.5161
rs6069499 20 53973735 A/G CBLN4 9.80×10-5 0.2857 0.1478?0.5521
rs6035200 20 18970894 A/T C20orf79///SLC24A3 9.66×10-5 0.5884 0.4395?0.7879
rs6064290 20 53890201 C/T Cerebellin-4 precursor 1.56×10-4 1.5401 1.1458?2.0773
rs4811635 20 53864343 A/G Cerebellin-4 precursor 4.02×10-4 1.5202 1.1369?2.0292
rs1370271 20 53974426 A/G Envelope protein 3.85×10-4 0.3295 0.1767?0.6144
rs7732110 5 135547908 C/T TRPC7 6.07×10-4 0.6058 0.4505?0.8148
rs11242316 5 135547747 C/G TRPC7 5.07×10-4 1.6866 1.2560?2.2648
rs3734125 5 135551643 C/T TRPC7 3.94×10-4 1.7300 1.2873?2.3250
rs10045073 5 135557803 C/T TRPC7 6.34×10-4 1.7120 1.2740?2.3006
rs10041689 5 135565676 A/G TRPC7 1.61×10-4 1.7676 1.3141?2.3776
rs171101 5 135646103 C/G TRPC7 3.35×10-4 0.5696 0.4155?0.7809
rs7701815 5 135649997 A/C TRPC7 4.07×10-4 1.7555 1.2805?2.4067
rs1392170 5 135659201 A/C TRPC7 4.01×10-4 0.5806 0.4229?0.7970
rs950715 5 135708138 C/T TRPC7 1.63×10-4 0.5317 0.3784?0.7471
rs3777150 5 135705746 A/C TRPC7 3.48×10-4 0.5240 0.3655?0.7513
rs12515628 5 135712924 C/T TRPC7 1.49×10-4 1.8919 1.3443?2.6624
rs346644 5 135746033 A/G TRPC7 3.48×10-4 0.5538 0.3955?0.7755
rs2548979 5 135481392 C/T SMAD5 5.24×10-4 0.5924 0.4408?0.7962
rs2906830 5 135481829 C/T SMAD5 8.77×10-4 1.6487 1.2284?2.2128
rs2548978 5 135492030 C/T SMAD5 3.86×10-4 1.7065 1.2701?2.2928
rs9327743 5 135495208 C/G SMAD5OS 3.21×10-4 0.5714 0.4243?0.7695
rs13187638 5 135500093 C/G SMAD5 9.59×10-4 1.6324 1.2146?2.1940
rs6596288 5 135512462 C/T SMAD5 3.82×10-4 1.7060 1.2702?2.2915
rs10056474 5 135519295 C/G SMAD5 3.82×10-4 1.7061 1.2702?2.2915
rs10064147 5 135533740 A/G SMAD5 1.67×10-4 1.7823 1.3249?2.3976
rs6886699 5 135543637 C/T SMAD5 2.03×10-4 1.7546 1.3037?2.3614
rs7719008 5 164000000 A/G 9.67×10-5 0.5480 0.4086?0.7348
Tab.3  Information on SNP Loci at Associated Genes (n=358)
Fig.2  Pvalue of all SNPs loci distribution on each chromosome.
MAF OR P
Case Control
GWAS (358) 0.11 (179) 0.03 (179) 0.29 9.80×10−5
Replication 1 (R1) (316) 0.10 (158) 0.04 (158) 0.37 4.01×10−4
Replication 2 (R2) (382) 0.10 (191) 0.03 (191) 0.23 5.67×10−5
Combined (1056) 0.10 (528) 0.03 (528) 0.29 6.37×10−10
Tab.4  Association of SNP rs6069499 within the CBLN4 Gene with Accident Proneness in the GWAS and the Replication Studies
Fig.3  Association scatter plot for the accident proneness susceptibility locus.
Neurotransmitters and hormones Unit Case group(179) Control group(179) P
Triiodothyronine (T3) ng/mL 1.06±0.14 1.11±0.20 0.38
Tetraiodothyronine (T4) ng/mL 82.63±23.02 87.01±23.87 0.50
testosterone (T) ng/mL 3.65±1.57 4.33±2.19 0.10
estradiol (E2) pg/mL 42.53±15.75 43.11±12.86 0.89
Corticotropin (ACTH) pg/mL 14.23±8.52 10.01±3.76 0.01**
Cortisol (Cor) ng/mL 147.48±31.95 155.91±24.60 0.38
Norepinephrine (NE) pmol/L 4424.85±2437.21 4927.11±1957.83 0.48
Dopamine (DA) ng/L 250.15±122.81 329.94±153.96 0.03**
5-hydroxytryptamine (5-HT) ng/L 2519.83±706.24 2042.47±857.90 0.57
g-aminobutyric acid (GABA) µmol/L 0.44±0.24 0.43±0.06 0.80
AngiotensinII (ANG-II) pg/mL 1064.77±220.37 1116.88±196.25 0.39
Dopamine-b-hydroxylase (DbH) ng/L 537.47±219.02 485.08±246.05 0.41
Tab.5  Comparison of Neurotransmitter and Hormone Levels in the Blood between Cases and Controls (n=358)
Fig.4  Three-dimensional threshold model of accident proneness.

s—Feature variables; e—Environmental variables; t—Period variables; P—Accident probability; a,b,g—Threshold of three variables (period, environment, and feature)

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