Causal relationship between neonatalhy perbilirubinemia and tic disorder by Mendelian randomization

doi:10.11852/zgetbjzz2023-1163

Abstract

Abstract: Objective To explore the causal relationship between neonatal hyperbilirubinemia and tic disorder (TD) by two-sample Mendelian randomized analysis (TSMR),in order to provide insights for the mechanism research of TD. Methods Data of genome-wide association study (GWAS) was used in this study.The exposure factor was neonatal hyperbilirubinemia,and the outcome variables were TD,multiple TD and vocal TD,respectively.Through MR analysis,inverse variance weighted (inverse-variance weighted,IVW) was used as the main analysis method, MR-Egger regression and weighted median (weighted median,WM) supplementary Methods were used to analyze the potential relationship between them.Cochran Q test and MR-Egger regression intercept were used to analyze the sensitivity. Results The inverse variance weighting method,showed that there was a potential causal relationship between neonatal hyperbilirubinemia and the risk of TD(OR=1.053,95%CI:1.006 - 1.102,P=0.024),but there was no potential causal correlation with other types of TD.Sensitivity analysis showed that there was no pleiotropy and heterogeneity(P>0.05),and the result was reliable. Conclusions There is a potential causal relationship between neonatal hyperbilirubinemia and TD,but the relationship needs to be further verified by a larger sample size.

Key words: neonatal hyperbilirubinemia, tic disorder, Mendelian randomization

摘要： 目的采用两样本孟德尔随机化(TSMR)分析法,探讨新生儿高胆红素血症与抽动障碍(TD)的因果关联,以期为TD的机制研究提供线索。方法利用全基因组关联研究(GWAS)的数据,暴露因素为新生儿高胆红素血症,结局变量分别为TD、短暂性TD和发声性TD,通过MR分析,将逆方差加权(IVW)作为主要分析方法,MR-Egger回归和加权中位数(WM)补充方法分析二者之间的潜在关系,利用Cochran Q检验、MR-Egger回归截距进行敏感性分析。结果逆方差加权法分析显示,新生儿高胆红素血症与TD发病风险之间存在潜在因果关系(OR=1.053,95%CI:1.006~1.102,P=0.024),但与其他类型抽动无潜在因果关联。敏感性分析显示不存在多效性和异质性(P>0.05),结果可靠。结论新生儿高胆红素血症与TD之间存在潜在因果关系,但二者关联需要更大样本量进一步验证。

关键词: 新生儿高胆红素血症, 抽动障碍, 孟德尔随机化

CLC Number:

R722.1

CUI Pengyuan, LI Guiping. Causal relationship between neonatalhy perbilirubinemia and tic disorder by Mendelian randomization[J]. Chinese Journal of Child Health Care, 2024, 32(10): 1116-1121.

崔鹏源, 李贵平. 孟德尔随机化法探究新生儿高胆红素血症与抽动障碍的因果关联[J]. 中国儿童保健杂志, 2024, 32(10): 1116-1121.

References

[1] 戎萍,马融,韩新民,等.中医儿科临床诊疗指南·抽动障碍(修订)[J].中医儿科杂志,2019,15(6):1-6.
Rong P,Ma R,Han XM,et al.Guideline for TCM pediatrics clinic diagnosis and treatment · tic disorder(amendment)[J].Journal of Pediatrics of Traditional Chinese Medicine,2019,15(6):1-6.(in Chinese)
[2] 姜妍琳,张蔷,翟睿,等.中国儿童抽动障碍患病率及危险因素系统评价[J].中国儿童保健杂志,2023,31(6):661-667.
Jiang YL,Zhang Q,Zhai R,et al.Systematic review of the prevalence and risk factors of tic disorders in Chinese children[J].Chin J Child Health Care,2023,31(6):661-667.(in Chinese)
[3] Vahia VN.Diagnostic and statistical manual of mental disorders 5:A quick glance[J].Indian J Psychiatry,2013,55(3):220-223.
[4] 路晨,郝宏文,廖欣婷,等.儿童抽动障碍致病危险因素的系统评价[J].中国循证医学杂志,2021,21(12):1407-1415.
Lu C,Hao HW,Liao XT,et al.Risk factors for children with tic disorder:A systematic review[J].Chinese Journal of Evidence-Based Medicine,2021,21(12):1407-1415.(in Chinese)
[5] 李志飞,汤晶晶,邹英杰,等.儿童抽动症相关因素的研究[J].中国妇幼健康研究,2016,27(1):20-22.
Li ZF,Tang JJ,Zou YJ,et al.Study on related factors of touratte syndrome[J].Chinese Journal of Woman and Child Health Research,2016,27(1):20-22.(in Chinese)
[6] Emdin CA,Khera AV,Kathiresan S.Mendelian randomization[J].JAMA,2017,318(19):1925-1926.
[7] 谭文岳,韦柏安,王树声,等.甲状腺功能障碍与前列腺癌的因果关联:两样本孟德尔随机化研究[J].重庆医科大学学报,2023,48(8):935-939.
Tan WY,Wei BA,Wang SS,et al.Casual relationship between thyroid dysfunction and prostate cancer:A two-sample Mendelian randomization study[J].Journal of Chongqing Medical University,2023,48(8):935-939.(in Chinese)
[8] Chen X,Yao T,Cai J,et al.Systemic inflammatory regulators and 7 major psychiatric disorders: A two-sample Mendelian randomization study[J].Prog Neuropsychopharmacol Biol Psychiatry,2022,116:110534.
[9] Burgess S,Butterworth A,Thompson SG.Mendelian randomization analysis with multiple genetic variants using summarized data[J].Genet Epidemiol,2013,37:658-665.
[10] Burgess S,Thompson SG.Interpreting findings from Mendelian randomization using the MR-Egger method[J].European Journal of Epidemiology,2017,32(5):377-389.
[11] Staley JR,Blackshaw J,Kamat MA,et al.Phenoscanner: A database of human genotype-phenotype associations[J].Bioinformatics,2016,32 (20):3207-3209.
[12] Diemer EW,Labrecque J,Tiemeier H,et al.Application of the instrumental inequalities to a mendelian randomization study with multiple proposed instruments[J].Epidemiology,2020,31 (1):65-74.
[13] Bowden J,Del Greco MF,Minelli C,et al.Improving the accuracy of two-sample summary-data Mendelian randomization: Moving beyond the NOME assumption[J].International Journal of Epidemiology,2018,48 (3):728-742.
[14] Bowden J,Del Greco MF,Minelli C,et al.A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization[J].Statistics in Medicine,2017,36 (11):1783-1802.
[15] Bowden J,Davey Smith G,Burgess S.Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression[J].Int J Epidemiol,2015,44(2):512-525.
[16] Pierce BL,Burgess S.Efficient design for Mendelian randomization studies: Subsample and 2-sample instrumental variable estimators[J].Am J Epidemiol,2013,178(7):1177-1184.
[17] 刘钊,王秋元,谢仟,等.2型糖尿病与年龄相关性黄斑变性之间的因果关系:一项孟德尔随机化研究[J].国际眼科杂志,2023,23(9):1573-1577.
Liu Z,Wang QY,Xie Q,et al.Causality between type 2 diabetes mellitus and age-related macular degeneration:A two-sample Mendelian randomization study[J].International Eye Science,2023,23(9):1573-1577.(in Chinese)
[18] 姚永新,王年美,邢晓华.小儿多发性抽动症临床特征及发病因素调查[J].中国妇幼保健,2019,34(23):5511-5513.
Yao YX,Wang NM,Xing XH,et al.Investigation on clinical characteristics and pathogenic factors of Tourette syndrome in children[J].Maternal and Child Health Care of China,2019,34(23):5511-5513.(in Chinese)
[19] 马霞霞,李红梅.产程中静滴缩宫素对新生儿黄疸的影响[J].延安大学学报(医学科学版),2015,13(1):40-42.
Ma XX,Li HM.Effects of oxytocin administrated by intravenous drip in labor on neonatal jaundice[J].Journal of Yan′an University(Socid Sciences Edition),2015,13(1):40-42.(in Chinese)
[20] 杜立中,马晓路.新生儿高胆红素血症诊断和治疗专家共识[J].中华儿科杂志,2014,52(10):745-748.
Du LZ,Ma XL.Expert consensus on diagnosis and treatment of neonatal hyperbilirubinemia[J].Chin J Pediatrics,2014,552 (10): 745-748.(in Chinese)
[21] Boskabadi H,Rakhshanizadeh F,Zakerihamidi M.Evaluation of maternal risk factors in neonatalhyperbilirubinemia[J].Arch Iran Med,2020,23(2):128-140.
[22] Mitra S,Rennie JM.Neonatal jaundice:Aetiology,diagnosis and treatment[J].British Journal of Hospital Medicine,2017,78 (12):699-704.
[23] Cayabyab R,Ramanathan R.High unbound bilirubin for age:A neurotoxin with major effects on the developing brain[J].Pediatr Res,2019,85 (2):183-190.
[24] Bhutani VK,Johnson-Hamerman L.The clinical syndrome of bilirubin-induced neurologic dysfunction[J].Semin Fetal Neonatal Med,2015,20 (1):6-13.
[25] Hsu CJ,Wong LC,Lee WT.Immunological dysfunction in Tourette syndrome and related disorders[J].Int J Mol Sci,2021,22 (2):853-853.
[26] 刘娣,张瑛.儿童抽动障碍研究进展[J].长治医学院学报,2022,36(3):237-240.
Liu D,Zhang Y.Research progress of tic disorder in children[J].Journal of Changzhi Medical College,2022,36(3):237-240.(in Chinese)
[27] Singer HS,Morris C,Grados M.Glutamatergic modulatory therapy for Tourette syndrome[J].Med Hypotheses,2010,74(5):862-867.
[28] 贾润梅,图雅,王育民.抽动障碍中枢神经递质失衡发病机制的研究进展[J].中国医药科学,2020,10(21):45-48.
Jia RM,Tu Y,Wang YM,et al.Research progress in the pathogenesis of central neurotransmitter imbalance in tic disorders[J].China Medicine and Pharmacy,2020,10(21):45-48.(in Chinese)
[29] Tomomi A,Junichi Y,Masatoshi N,et al.Astroglial glutamate transporter deficiency increases synaptic excitability and leads to pathological repetitive behaviors in mice[J].Neuropsychopharmacology,2015,40(7):1569-1579.
[30] 冯鹏,史正刚,孙治前,等.中医药调控神经递质治疗多发性抽动症的研究进展[J].中药药理与临床,2020,36(2):267-271.
Feng P,Shi ZG,Sun ZQ,et al.Research progress of Chinese medicine treating on touratte syndrome by regulating neurotransmitter[J].Pharmacology and Clinics of Chinese Materia Medica,2020,10(21):45-48.(in Chinese)