Genome-wide single nucleotide polymorphism heritability of nicotine dependence as a multidimensional phenotype

Abstract

Background Heritability estimates from twin studies of the multi-faceted phenotype of nicotine dependence (ND) range from moderate to high (31–60%), but vary substantially based on the specific ND-related construct examined. The current study estimated the aggregate role of common genetic variants on key ND constructs. Methods Genomic Relatedness Restricted Maximum Likelihood (GREML) was used to decompose phenotypic variance across multiple ND indices using 796,125 polymorphisms from 2346 unrelated “lifetime ever smokers” of European ancestry. Measures included DSM-IV ND and FTND summary measures and constituent constructs (e.g. withdrawal severity, tolerance, heaviness of smoking, and time spent smoking). Exploratory (EFA) and confirmatory (CFA) factor models were used to describe the covariance structure across ND measures; resulting factor(s) were the subject(s) of GREML analyses. Results Factor models indicated highly correlated DSM-IV and FTND factors for ND (0.545 [95% CI: 0.50–0.60]) that could be represented as a higher-order factor (NIC DEP). Additive genetic influences on NIC DEP was 33% (S.E.= .14, p = .009). Post hoc analyses indicated moderate genetic effects on the DSM-IV (34% [S.E.= .14, p = .008]) and FTND factors (26% [SE .=.14, p = .032]), both of which were influenced by the same genetic effects, (rG-SNP = 1.00, S.E. = .09, p < .00001). Conclusions Overall, common SNPs accounted for a large proportion of the genetic influences on ND-related phenotypes that have been observed in twin studies. Genetic contributions across distinct ND scales were largely influenced by shared genetic factors.

Neurogenetic determinants and mechanisms of addiction to nicotine and smoked tobacco

“…Also using SNP data, Bidwell et al . () estimated that a nicotine dependence measure, constructed from DSM‐IV and FTND scores, has an h 2 of 0.33. Together, these studies confirm the contribution of genetic factors in various stages of smoking behavior.…”

“…In a study of twin pairs, Xian et al (2003) reported that genetic influences accounted for 54% and 29.7% of the variance in risk for failed smoking cessation and nicotine withdrawal, respectively. Also using SNP data, Bidwell et al (2016) estimated that a nicotine dependence measure, constructed from DSM-IV and FTND scores, has an h 2 of 0.33. Together, these studies confirm the contribution of genetic factors in various stages of smoking behavior.…”

“…In addition to FTND, nicotine dependence is also measured using other instruments, such as the Diagnostic and Statistical Manual (i.e., DSM, III, IIIR, IV or V editions)-based criteria, the Wisconsin Inventory of Smoking Dependence Motives (WISDM), or simply the number of cigarettes per day (CPD), which is also part of the FTND. Although there is large overlap between these measures, studies indicate that they are probably measuring different phenotypes involved in nicotine dependence (Bidwell et al, 2016). A number of novel statistical methods that consider the joint effect of multiple variants on multiple phenotypes are being developed.…”

Habenular and striatal activity during performance feedback are differentially linked with state-like and trait-like aspects of tobacco use disorder

“…In the context of cigarette smoking, addiction severity is typically quantified with the 6-item FTND [87]. FTND scores are highly heritable [88] and routinely utilized as a primary phenotype in studies linking smoking behaviors with nicotinic acetylcholine receptor and other genetic variants [89]. As such, we conceptualized FTND scores (range: 1-10) collected during the orientation visit as a trait-level measure of nicotine addiction severity.…”

Association of opioid receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) with nicotine dependence

“…Smoking is considered to be one of the independent causes of a series of severe illnesses such as stroke, pulmonary disease, cardiac-cerebral vascular disease, and cancer. In recent years, some studies implicate genetic factors in the susceptibility to smoking addiction [ 2 , 3 ]. A number of candidate genes in the reinforcement and reward system may play vital roles in drug abuse, including that of nicotine dependence [ 4 ].…”