ArticlePloS one2012
Comprehensive phenotype/genotype analyses of the norepinephrine transporter gene (SLC6A2) in ADHD: relation to maternal smoking during pregnancy.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00483106 (Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder), which is not on this map. Cited by 14 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)
Who cites it
14 citing papers in PubMed, 3 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD).The Cochrane database of systematic reviews · 2023Pooled it
- Pooled it
- Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD).The Cochrane database of systematic reviews · 2015Pooled it
- Roles of Single Nucleotide Polymorphisms in the SLC6A2 Gene in the Risk of Vasovagal Syncope Among Children in Eastern China: A Case-Control Study.Health science reports · 2025Article
- Association between maternal smoking during pregnancy and learning disabilities in children and adolescents: A propensity score matching analysis.Tobacco induced diseases · 2025Article
- The roles of familial transmission and smoking during pregnancy on executive function skills: A sibling-comparison study.Development and psychopathology · 2022Article
- CES1 and SLC6A2 Genetic Variants As Predictors of Response To Methylphenidate in Autism Spectrum Disorders.Pharmacogenomics and personalized medicine · 2022Article
- DNA methylome perturbations: an epigenetic basis for the emergingly heritable neurodevelopmental abnormalities associated with maternal smoking and maternal nicotine exposure†.Biology of reproduction · 2021Review
- Facing the Methodological Challenge in Dissecting the Genetics of ADHD: A Case for Deep Phenotyping and Heterogeneity Reduction.Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent · 2020Article
- Effects of norepinephrine transporter gene variants on NET binding in ADHD and healthy controls investigated by PET.Human brain mapping · 2016Article
- Sex differences in DNA methylation assessed by 450 K BeadChip in newborns.BMC genomics · 2015Article
- Article
- The norepinephrine transporter in attention-deficit/hyperactivity disorder investigated with positron emission tomography.JAMA psychiatry · 2014Article
- Cognitive function, health-related quality of life, and symptoms of depression and anxiety sensitivity are impaired in patients with the postural orthostatic tachycardia syndrome (POTS).Frontiers in physiology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveDespite strong pharmacological evidence implicating the norepinephrine transporter in ADHD, genetic studies have yielded largely insignificant results. We tested the association between 30 tag SNPs within the SLC6A2 gene and ADHD, with stratification based on maternal smoking during pregnancy, an environmental factor strongly associated with ADHD.
methodsChildren (6-12 years old) diagnosed with ADHD according to DSM-IV criteria were comprehensively evaluated with regard to several behavioral and cognitive dimensions of ADHD as well as response to a fixed dose of methylphenidate (MPH) using a double-blind placebo controlled crossover trial. Family-based association tests (FBAT), including categorical and quantitative trait analyses, were conducted in 377 nuclear families.
resultsA highly significant association was observed with rs36021 (and linked SNPs) in the group where mothers smoked during pregnancy. Association was noted with categorical DSM-IV ADHD diagnosis (Z=3.74, P=0.0002), behavioral assessments by parents (CBCL, P=0.00008), as well as restless-impulsive subscale scores on Conners'-teachers (P=0.006) and parents (P=0.006). In this subgroup, significant association was also observed with cognitive deficits, more specifically sustained attention, spatial working memory, planning, and response inhibition. The risk allele was associated with significant improvement of behavior as measured by research staff (Z=3.28, P=0.001), parents (Z=2.62, P=0.009), as well as evaluation in the simulated academic environment (Z=3.58, P=0.0003).
conclusionsBy using maternal smoking during pregnancy to index a putatively more homogeneous group of ADHD, highly significant associations were observed between tag SNPs within SLC6A2 and ADHD diagnosis, behavioral and cognitive measures relevant to ADHD and response to MPH. This comprehensive phenotype/genotype analysis may help to further understand this complex disorder and improve its treatment. Clinical trial registration information - Clinical and Pharmacogenetic Study of Attention Deficit with Hyperactivity Disorder (ADHD); www.clinicaltrials.gov; NCT00483106.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.