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LPHN3 gene variations and susceptibility to ADHD in Chinese Han population: a two-stage case-control association study and gene-environment interactions.
Eur Child Adolesc Psychiatry 2019; 28(6):861-873EC

Abstract

Polymorphisms in latrophilin 3 (LPHN3) were recently reported to be associated with attention-deficit/hyperactivity disorder (ADHD), and subsequently other researchers tried to replicate the findings in different populations. This study was aimed to confirm the role of the LPHN3 in ADHD and explore the potential interactions with environmental risk factors in Chinese Han population. We examined the association of LPHN3 with ADHD in a population of 473 ADHD children and 585 controls. As a supplement of ADHD diagnosis, Conners Parent Symptom Questionnaire (PSQ) was used to evaluate ADHD symptoms. Blood lead levels (BLLs) were measured by atomic absorption spectrophotometry and other potential environmental risk factors were determined via a questionnaire filled out by the parents. Finally, after validation in an independent sample (284 cases and 390 controls), we observed significant associations between LPHN3 variants rs1868790 and ADHD risk in combined stage within codominant model [TA/AA: OR (95% CI) = 1.636 (1.325-2.021)], dominant model [OR (95% CI) = 1.573 (1.288-1.922)], and additive model [OR (95% CI) = 1.535 (1.266-1.862)]. Furthermore, rs1868790 significantly interacted with BLLs and maternal stress to modify ADHD susceptibility (P < 0.05), and rs1868790 was found to be related with ADHD symptoms (P < 0.05). Expression quantitative trait loci analysis further indicated that rs1868790 took part in the regulation of LPHN3 gene expression. As the first study to comprehensively explore the role of LPHN3 in ADHD in Chinese children, our research suggests that LPHN3 gene has a significant effect on the ADHD in a Chinese population.

Authors+Show Affiliations

Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, People's Republic of China. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, People's Republic of China. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, People's Republic of China. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, People's Republic of China. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, People's Republic of China. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, People's Republic of China. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, People's Republic of China. wujingtj@hust.edu.cn. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. wujingtj@hust.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30406846

Citation

Huang, Xin, et al. "LPHN3 Gene Variations and Susceptibility to ADHD in Chinese Han Population: a Two-stage Case-control Association Study and Gene-environment Interactions." European Child & Adolescent Psychiatry, vol. 28, no. 6, 2019, pp. 861-873.
Huang X, Zhang Q, Gu X, et al. LPHN3 gene variations and susceptibility to ADHD in Chinese Han population: a two-stage case-control association study and gene-environment interactions. Eur Child Adolesc Psychiatry. 2019;28(6):861-873.
Huang, X., Zhang, Q., Gu, X., Hou, Y., Wang, M., Chen, X., & Wu, J. (2019). LPHN3 gene variations and susceptibility to ADHD in Chinese Han population: a two-stage case-control association study and gene-environment interactions. European Child & Adolescent Psychiatry, 28(6), pp. 861-873. doi:10.1007/s00787-018-1251-8.
Huang X, et al. LPHN3 Gene Variations and Susceptibility to ADHD in Chinese Han Population: a Two-stage Case-control Association Study and Gene-environment Interactions. Eur Child Adolesc Psychiatry. 2019;28(6):861-873. PubMed PMID: 30406846.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LPHN3 gene variations and susceptibility to ADHD in Chinese Han population: a two-stage case-control association study and gene-environment interactions. AU - Huang,Xin, AU - Zhang,Qi, AU - Gu,Xue, AU - Hou,Yuwei, AU - Wang,Min, AU - Chen,Xinzhen, AU - Wu,Jing, Y1 - 2018/11/08/ PY - 2018/03/28/received PY - 2018/10/31/accepted PY - 2018/11/9/pubmed PY - 2019/8/14/medline PY - 2018/11/9/entrez KW - Association study KW - Attention-deficit/hyperactivity disorder KW - Gene–environment interaction KW - LPHN3 SP - 861 EP - 873 JF - European child & adolescent psychiatry JO - Eur Child Adolesc Psychiatry VL - 28 IS - 6 N2 - Polymorphisms in latrophilin 3 (LPHN3) were recently reported to be associated with attention-deficit/hyperactivity disorder (ADHD), and subsequently other researchers tried to replicate the findings in different populations. This study was aimed to confirm the role of the LPHN3 in ADHD and explore the potential interactions with environmental risk factors in Chinese Han population. We examined the association of LPHN3 with ADHD in a population of 473 ADHD children and 585 controls. As a supplement of ADHD diagnosis, Conners Parent Symptom Questionnaire (PSQ) was used to evaluate ADHD symptoms. Blood lead levels (BLLs) were measured by atomic absorption spectrophotometry and other potential environmental risk factors were determined via a questionnaire filled out by the parents. Finally, after validation in an independent sample (284 cases and 390 controls), we observed significant associations between LPHN3 variants rs1868790 and ADHD risk in combined stage within codominant model [TA/AA: OR (95% CI) = 1.636 (1.325-2.021)], dominant model [OR (95% CI) = 1.573 (1.288-1.922)], and additive model [OR (95% CI) = 1.535 (1.266-1.862)]. Furthermore, rs1868790 significantly interacted with BLLs and maternal stress to modify ADHD susceptibility (P < 0.05), and rs1868790 was found to be related with ADHD symptoms (P < 0.05). Expression quantitative trait loci analysis further indicated that rs1868790 took part in the regulation of LPHN3 gene expression. As the first study to comprehensively explore the role of LPHN3 in ADHD in Chinese children, our research suggests that LPHN3 gene has a significant effect on the ADHD in a Chinese population. SN - 1435-165X UR - https://www.unboundmedicine.com/medline/citation/30406846/LPHN3_gene_variations_and_susceptibility_to_ADHD_in_Chinese_Han_population:_a_two_stage_case_control_association_study_and_gene_environment_interactions_ L2 - https://dx.doi.org/10.1007/s00787-018-1251-8 DB - PRIME DP - Unbound Medicine ER -