Background: Pharmacologic and animal studies have strongly implicated the norepinephrine transporter (NET) in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We conducted a family-based study, with stratification based on sex and subtype, to test the association between 30 tag single-nucleotide polymorphisms (SNPs) within the gene encoding NET (SLC6A2) and ADHD.
Methods: Family-based association tests were conducted with the categorical diagnosis of ADHD, as well as quantitative phenotypes of clinical relevance (Conners Global Index for Teachers and Parents, and Child Behavior Checklist measures). Sliding window haplotype analysis was conducted with screening based on conditional power using PBAT.
Results: A previously reported association with rs3785143 was confirmed in this study. Further, extensive association was observed with haplotype blocks, with a differential pattern observed based on sex and subtype. The 5' region of the gene (encompassing haplotype block 1 and including a functional promoter SNP, rs28386840) showed an association with ADHD in girls (irrespective of subtype). A different region of the gene (distributed around haplo-type block 2) was associated with distinct behavioural phenotypes in boys. These findings are correlated with previously reported functional studies of gene variants in SLC6A2.
Limitations: The most important limitation of the study is the small size of the groups resulting from the stratification based on sex followed by subtype.
Conclusion: The results obtained in this family-based study suggest that haplotype blocks within different regions of SLC6A2 show differential association with the disorder based on sex and subtype. These associations may have been masked in previous studies when tests were conducted with pooled samples.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3297073 | PMC |
| http://dx.doi.org/10.1503/jpn.110073 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dementia Care Research and Psychosocial Factors.
Alzheimers Dement
December 2024
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
Background: Prior research has demonstrated the positive association between social support and cognition. Specifically, greater social support has been linked with improved cognitive performance and reduced risk of dementia. In particular, emotional support has been identified as a key dimension in the relationship between social support and cognition.
View Article and Find Full Text PDFTechnology and Dementia Preconference.
Alzheimers Dement
December 2024
Newcastle University, Newcastle, Tyne and Wear, UK.
Background: Digital mobility outcomes (DMOs) can be captured using body-worn inertial measurement units (IMUs) in lab-based and real-world environments. DMOs may support differential diagnosis of dementia; for example, Alzheimer's disease (AD) and Lewy body disease (LBD) show unique signatures of gait impairment. Growing evidence suggests that turning impairments are related to cognitive decline.
View Article and Find Full Text PDFRecipient sex and donor leukemic cell characteristics determine leukemogenesis in patient-derived models.
Haematologica
January 2025
University Clinic Tübingen, Department for Internal Medicine II, University of Tübingen, Tübingen, Germany; German Cancer Consortium (DKTK), partner site Tübingen, a partnership between DKFZ and University Hospital Tübingen.
In acute myeloid leukemia (AML), leukemogenesis depends on cell-intrinsic genetic aberrations and thus, studies on AML require investigations in an in vivo setting as provided by patient derived xenografts (PDX) models. Here we report that, next to leukemic cell characteristics, recipient sex highly influences the outgrowth of AML cells in PDX models, with females being much better repopulated than males in primary as well as secondary transplantation assays. Testosterone may be the more important player since, strikingly, better engraftment was seen in castrated versus control male recipients, while ovariectomy did not significantly impair engraftment in females.
View Article and Find Full Text PDFClinical characteristics of hospitalized male adolescents and young adults with avoidant/restrictive food intake disorder (ARFID).
J Eat Disord
January 2025
Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
Background: Avoidant/restrictive food intake disorder (ARFID) may result in significant medical sequelae. Compared to youth with eating disorders like anorexia nervosa (AN), youth with ARFID tend to be younger and are more likely to be male. We aim to describe sex differences in clinical characteristics of youth hospitalized for medical complications of ARFID and compare their characteristics with youth hospitalized for anorexia nervosa.
View Article and Find Full Text PDFAssociation of Systemic Thromboxane Generation With Risk of Developing Heart Failure.
J Am Coll Cardiol
January 2025
Division of Biostatistics and Health Services Research, Department of Population and Quantitative Health Sciences, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Background: Systemic thromboxane A generation, which is readily assessed by quantifying thromboxane B metabolites (TXB-M) in the urine, is associated with impaired cardiac performance and mortality in aspirin (ASA) users with heart failure (HF).
Objectives: This study sought to determine the association of urinary TXB-M with the risk of developing HF in individuals without prior history of HF and with normal left ventricular function irrespective of ASA use.
Methods: Urine TXB-M were measured by immunoassay and adjusted to urine concentration and renal function (TXB-M) in 2,611 Framingham Heart Study participants (54.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!