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

被引:17
作者
Bidwell, L. C. [1 ,2 ,3 ]
Palmer, R. H. C. [2 ,3 ]
Brick, L. [3 ]
McGeary, J. E. [2 ,3 ,4 ]
Knopik, V. S. [2 ,3 ]
机构
[1] Univ Colorado, Inst Cognit Sci, Boulder, CO 80309 USA
[2] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Providence, RI 02912 USA
[3] Rhode Isl Hosp, Dept Psychiat, Div Behav Genet, Providence, RI USA
[4] Providence VA Med Ctr, Dept Vet Affairs, Providence, RI USA
基金
美国国家卫生研究院;
关键词
Addiction; genetics; single nucleotide polymorphism heritability; substance dependence; TOBACCO DEPENDENCE; SMOKING INITIATION; ALCOHOL DEPENDENCE; MAJOR DEPRESSION; FAGERSTROM TEST; GENETICS; TWIN; VULNERABILITY; CIGARETTES; ADOLESCENT;
D O I
10.1017/S0033291716000453
中图分类号
B849 [应用心理学];
学科分类号
040203 ;
摘要
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. Method. Genomic-relationship-matrix 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 Fagerstrom Test for Nicotine Dependence (FTND) summary measures and constituent constructs (e.g. withdrawal severity, tolerance, heaviness of smoking and time spent smoking). Exploratory and confirmatory 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% confidence interval 0.50-0.60) that could be represented as a higher-order factor (NIC DEP). Additive genetic influence on NIC DEP was 33% (S.E. = 0.14, p = 0.009). Post-hoc analyses indicated moderate genetic effects on the DSM-IV (34%, S.E. = 0.14, p = 0.008) and FTND (26%, S.E. = 0.14, p = 0.032) factors, both of which were influenced by the same genetic effects (rG-SNP = 1.00, S.E. = 0.09, p < 0.00001). Conclusions. Overall, common single nucleotide polymorphisms 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.
引用
收藏
页码:2059 / 2069
页数:11
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