European Child & Adolescent Psychiatry

, Volume 28, Issue 6, pp 861–873 | Cite as

LPHN3 gene variations and susceptibility to ADHD in Chinese Han population: a two-stage case–control association study and gene–environment interactions

  • Xin Huang
  • Qi Zhang
  • Xue Gu
  • Yuwei Hou
  • Min Wang
  • Xinzhen Chen
  • Jing WuEmail author
Original Contribution


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.


Attention-deficit/hyperactivity disorder LPHN3 Association study Gene–environment interaction 



We are sincerely grateful to the participating families for their cooperation. We thank Dr. Jun Lin from Wuhan Medical and Health Center for Women and Children, and Dr. Yan Zhong from Children’s Hospital of Hunan province for their widespread support for our study and sharing their knowledge. This work was supported partially by the National Natural Science Foundation of China (81773456), the Fundamental Research Funds for the Central Universities, HUST (2016 YXMS218) supported Dr. Jing Wu.

Compliance with ethical standards

Conflict of interest

The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments. Informed consent was obtained from all individual participants included in the study.

Supplementary material

787_2018_1251_MOESM1_ESM.docx (276 kb)
Supplementary material 1 (DOCX 275 kb)


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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, School of Public Health, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  2. 2.Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China

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