How to Cite this Article: Das D, Tan X, Easteal S. 2011. Effect of model choice in genetic association studies: DRD4 exon III VNTR and cigarette use in young adults. Am J Med Genet Part B 156:346–351.
Effect of model choice in genetic association studies: DRD4 exon III VNTR and cigarette use in young adults†
Article first published online: 13 JAN 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 156, Issue 3, pages 346–351, April 2011
How to Cite
Das, D., Tan, X. and Easteal, S. (2011), Effect of model choice in genetic association studies: DRD4 exon III VNTR and cigarette use in young adults. Am. J. Med. Genet., 156: 346–351. doi: 10.1002/ajmg.b.31169
- Issue published online: 11 MAR 2011
- Article first published online: 13 JAN 2011
- Manuscript Accepted: 14 DEC 2010
- Manuscript Received: 24 MAY 2010
- National Health and a Medical Council of Australia (Unit Grant 973302, Program Grant 179805, Project Grant 418039)
- Capacity Building Grant in Population Health Research. Grant Number: 418020
- dopamine D4 receptor;
- variable number tandem repeat;
- cigarettes per day;
- genetic models
A major concern with the vast literature associating the highly polymorphic 48 bp VNTR in exon III of the human dopamine receptor D4 gene (DRD4) with various behavioral phenotypes is the lack of concordance between studies. Part of the problem arises from the absence of a universally accepted scheme for pooling the large number of low frequency genotypes into appropriate categories. Here, we investigated the effect of different pooling strategies and genetic models on the reported association between DRD4-exIII-VNTR polymorphism and cigarette smoking. Genotyping was performed on a large randomly selected community-based sample of 2,274 individuals aged 20–24 years. Participants were grouped into sub-samples based on their genotypes to test specific genetic models. Multiple regression analyses were used to assess the relationship between DRD4-exIII-VNTR genotype and cigarette smoking measures while controlling for confounders. While smoking status and age at start of smoking were not associated with the genotype, a significantly (P = 0.006) higher rate of cigarette consumption was observed among carriers of the 7-repeat (7r) allele. Thus, 7r carriers were not more likely to be smokers but if they did smoke they consumed significantly more cigarettes per day than 4r carriers. Unlike previous studies this association was observed only when comparing carriers of the 7r with the 4r but not the other repeat alleles. Our study demonstrates the need for caution when grouping functionally different DRD4-exIII-VNTR alleles in association studies. It particularly highlights the requirement for better functional characterization of the DRD4-exIII-VNTR alleles for interpreting results from association studies. © 2011 Wiley-Liss, Inc.