Gene-Gene Interactions Among CHRNA4, CHRNB2, BDNF, and NTRK2 in Nicotine Dependence

Li, Ming D.; Lou, Xiang Yang; Chen, Guo-Bo; Jennie, Z.; Elston, Robert C.

doi:10.1016/j.biopsych.2008.04.026

Cited by 60 publications

(45 citation statements)

References 48 publications

(62 reference statements)

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“…They also reported no significant association for each individual gene. Furthermore, gene-gene interactions were reported for nicotine dependence among CHRNA4, CHRNB2, brain-derived neurotrophic factor, and neurotrophic tyrosine kinase receptor 2 genes in a case-control study [Li et al, 2008].…”

Section: Discussionmentioning

confidence: 98%

Detection of SNP‐SNP interactions in trios of parents with schizophrenic children

Fallin

Louis

et al. 2010

Genetic Epidemiology

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Schizophrenia (SZ) is a heritable and complex psychiatric disorder with an estimated worldwide prevalence of about 1%. Research on the risk factors for SZ has thus far yielded few clues to causes, but has pointed to a heterogeneous etiology that likely involves multiple genes and gene-environment interactions. In this manuscript, we apply a novel method (trio logic regression, Li et al., 2009) to case-parent trio data from a SZ candidate gene study conducted on families of Ashkenazi Jewish descent, and demonstrate the method's ability to detect multi-gene models for SZ risk in the family-based design. In particular, we demonstrate how this method revealed a genotype-phenotype association that includes an allele without marginal effect.

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Section: Discussionmentioning

confidence: 98%

Detection of SNP‐SNP interactions in trios of parents with schizophrenic children

Fallin

Louis

et al. 2010

Genetic Epidemiology

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“…Conventional single-gene association analysis may not be useful in the case of CHRNB2 and its role in ND genetic would need to be analyzed jointly with other genes. 119 Other nAChR loci Compared with the data regarding the four loci presented above, less evidence supports involvement of four other nAChR loci (CHRNA2, CHRNA7, CHRNA9 and CHRNA10) in genetic susceptibility to ND.…”

Section: Genetic Variation In Multiple Brain Nachrs and Nd L Greenbaumentioning

confidence: 90%

“…119 The importance of these findings lies in the notion that although a contribution of CHRNB2 to ND may not be observed when this gene is analyzed separately, it may still be involved in ND, due to dependency of a CHRNB2 effect on specific variants in other genes (CHRNA4 or NTRK2). Conventional single-gene association analysis may not be useful in the case of CHRNB2 and its role in ND genetic would need to be analyzed jointly with other genes.…”

Section: Genetic Variation In Multiple Brain Nachrs and Nd L Greenbaumentioning

confidence: 98%

Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions

Greenbaum¹,

Lerer²

2009

Mol Psychiatry

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Nicotine dependence (ND), a major public health challenge, is a complex, multifactorial behavior, in which both genetic and environmental factors have a role. Brain nicotinic acetylcholine receptor (nAChR)-encoding genes are among the most prominent candidate genes studied in the context of ND, because of their biological relevance as binding sites for nicotine. Until recently, most research on the role of nAChRs in ND has focused on two of these genes (encoding the a4-and b2-subunits) and not much attention has been paid to the possible contribution of the other nine brain nAChR subunit genes (a2-a3, a5-a7, a9-a10, b3-b4) to the pathophysiology and genetics of ND. This situation has changed dramatically in the last 2 years during which intensive research had addressed the issue, mainly from the genetics perspective, and has shown the importance of the CHRNA5-CHRNA3-CHRNB4 and CHRNA6-CHRNB3 loci in ND-related phenotypes. In this review, we highlight recent findings regarding the contribution of non-a4/b2-subunit containing nAChRs to ND, based on several lines of evidence: (1) human genetics studies (including linkage analysis, candidate-gene association studies and whole-genome association studies) of several ND-related phenotypes; (2) differential pharmacological and biochemical properties of receptors containing these subunits; (3) evidence from genetically manipulated mice; and (4) the contribution of nAChR genes to ND-related personality traits and neurocognitive profiles. Combining neurobiological genetic and behavioral perspectives, we suggest that genetic susceptibility to ND is not linked to one or two specific nAChR subtype genes but to several. In particular, the a3, a5-6 and b3-4 nAChR subunit-encoding genes may play a much more pivotal role in the neurobiology and genetics of ND than was appreciated earlier. At the functional level, variants in these subunit genes (most likely regulatory) may have independent as well as interactive contributions to the ND phenotype spectrum. We address methodological challenges in the field, highlight open questions and suggest possible pathways for future research.

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“…Studies of human subjects addicted to cigarette smoking reveal association with several BDNF SNPs (Beuten et al, 2005) including the V66M polymorphism (Lang et al, 2007b) as well as TrkB SNPs (Beuten et al, 2007), suggesting that humans with altered BDNF signaling may be more likely to become addicted and remain addicted to nicotine. A recent meta-analysis suggests that several BDNF SNPs are significantly correlated to initiation of smoking (Numan et al, 1998) Gene interaction studies suggest that a potential explanation for this association may be the influence of BDNF-TrkB signaling on regulation of nicotinic receptor subunits ␣4 and ␤2 (Li et al, 2008).…”

Section: Nicotine and Alcoholmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders

Autry

Monteggia²

2012

Pharmacol Rev

1,162

764

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Gene-Gene Interactions Among CHRNA4, CHRNB2, BDNF, and NTRK2 in Nicotine Dependence

Cited by 60 publications

References 48 publications

Detection of SNP‐SNP interactions in trios of parents with schizophrenic children

Detection of SNP‐SNP interactions in trios of parents with schizophrenic children

Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions

Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders

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