Article

Genome-wide Association Study of Smoking Initiation and Current Smoking

Department of Biological Psychology, Center for Neurogenomic and Cognitive Research, VU University Amsterdam, The Netherlands.
The American Journal of Human Genetics (Impact Factor: 10.99). 04/2009; 84(3):367-79. DOI: 10.1016/j.ajhg.2009.02.001
Source: PubMed

ABSTRACT For the identification of genes associated with smoking initiation and current smoking, genome-wide association analyses were carried out in 3497 subjects. Significant genes that replicated in three independent samples (n = 405, 5810, and 1648) were visualized into a biologically meaningful network showing cellular location and direct interaction of their proteins. Several interesting groups of proteins stood out, including glutamate receptors (e.g., GRIN2B, GRIN2A, GRIK2, GRM8), proteins involved in tyrosine kinase receptor signaling (e.g., NTRK2, GRB14), transporters (e.g., SLC1A2, SLC9A9) and cell-adhesion molecules (e.g., CDH23). We conclude that a network-based genome-wide association approach can identify genes influencing smoking behavior.

Download full-text

Full-text

Available from: Henning Tiemeier, Jun 20, 2015
0 Followers
 · 
106 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: The glutamate receptor, metabotropic 8 gene (GRM8) encodes a G-protein-coupled glutamate receptor and has been associated with smoking behavior and liability to alcoholism implying a role in addiction vulnerability. Data from animal studies suggest that GRM8 may be involved in the regulation of the neuropeptide Y and melanocortin pathways and might influence food intake and metabolism. This study aimed to investigate the effects of the genetic variant rs2237781 within GRM8 on human eating behavior. Methods: The ini- tial analysis included 548 Sorbs from Germany who have been extensively phe- notyped for metabolic traits and who completed the German version of the three-factor eating questionnaire. In addition, we analyzed two independent sample sets comprising 293 subjects from another German cohort and 430 Old Order Amish individuals. Genetic associations with restraint, disinhibition, and hunger were assessed in an additive linear regression model. Results: Among the Sorbs the major G allele of rs2237781 was significantly associated with increased restraint scores in eating behavior (P = 1.9 9 10?4; b =+1.936). The German cohort and the Old Order Amish population revealed a trend in the same direction for restraint (P = 0.242; b =+0.874; P = 0.908; b =+0.096; respectively). A meta-analysis resulted in a combined P = 3.1 9 10?3 (Z-score 2.948). Conclusion: Our data suggest that rs2237781 within GRM8 may influ- ence human eating behavior factors probably via pathways involved in addictive behavior.
    09/2013; 3(5):n/a-n/a. DOI:10.1002/brb3.151
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the past 25 years, the Adult Netherlands Twin Register (ANTR) has collected a wealth of information on physical and mental health, lifestyle, and personality in adolescents and adults. This article provides an overview of the sources of information available, the main research findings, and an outlook for the future. Between 1991 and 2012, longitudinal surveys were completed by twins, their parents, siblings, spouses, and offspring. Data are available for 33,957 participants, with most individuals having completed two or more surveys. Smaller projects provided in-depth phenotyping, including measurements of the autonomic nervous system, neurocognitive function, and brain imaging. For 46% of the ANTR participants, DNA samples are available and whole genome scans have been obtained in more than 11,000 individuals. These data have resulted in numerous studies on heritability, gene x environment interactions, and causality, as well as gene finding studies. In the future, these studies will continue with collection of additional phenotypes, such as metabolomic and telomere length data, and detailed genetic information provided by DNA and RNA sequencing. Record linkage to national registers will allow the study of morbidity and mortality, thus providing insight into the development of health, lifestyle, and behavior across the lifespan.
    Twin Research and Human Genetics 01/2013; DOI:10.1017/thg.2012.140 · 1.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although many genetic association studies have been carried out, it remains unclear which genes contribute to depression. This may be due to heterogeneity of the DSM-IV category of depression. Specific symptom-dimensions provide a more homogenous phenotype. Furthermore, as effects of individual genes are small, analysis of genetic data at the pathway-level provides more power to detect associations and yield valuable biological insight. In 1,398 individuals with a Major Depressive Disorder, the symptom dimensions of the tripartite model of anxiety and depression, General Distress, Anhedonic Depression, and Anxious Arousal, were measured with the Mood and Anxiety Symptoms Questionnaire (30-item Dutch adaptation; MASQ-D30). Association of these symptom dimensions with candidate gene sets and gene sets from two public pathway databases was tested using the Global test. One pathway was associated with General Distress, and concerned molecules expressed in the endoplasmatic reticulum lumen. Seven pathways were associated with Anhedonic Depression. Important themes were neurodevelopment, neurodegeneration, and cytoskeleton. Furthermore, three gene sets associated with Anxious Arousal regarded development, morphology, and genetic recombination. The individual pathways explained up to 1.7% of the variance. These data demonstrate mechanisms that influence the specific dimensions. Moreover, they show the value of using dimensional phenotypes on one hand and gene sets on the other hand.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 07/2012; 159B(5):519-28. DOI:10.1002/ajmg.b.32058 · 3.27 Impact Factor