T. Korhonen

Smoking strongly predicts disability retirement due to COPD: the Finnish Twin Cohort Study

No previous studies on the association of smoking behaviour with disability retirement due to register verified chronic obstructive pulmonary disease (COPD) exist. This 30-yr follow-up study examined how strongly aspects of cigarette smoking predict disability retirement due to COPD. The study population consisted of 24,043 adult Finnish twins (49.7% females) followed from 1975 to 2004. At baseline the participants had responded to a questionnaire. Information on retirement was obtained from the Finnish pension registers. Smoking strongly predicted disability retirement due to COPD. In comparison to never-smokers, age adjusted hazard ratio (HR) for current smokers was 22.0 (95% CI 10.0–48.5) and for smokers with ≥12 pack-yrs was 27.3 (95% CI 12.6–59.5). Similar estimates of risk were observed in within-pair analyses of twin pairs discordant for disability retirement due to COPD. Among discordant monozygotic pairs those with disability pension due to COPD were more often current smokers. The effect of early smoking onset (<18 yrs) on the risk of disability retirement due to COPD remained after adjustment for the amount smoked (HR 1.70, 95% CI 1.08–2.68). Smoking strongly predicts disability retirement due to COPD. Preventive measures against disability retirement and other harmful consequences of tobacco smoking should receive greater emphasis.

Neuregulin signaling pathway in smoking behavior

Understanding molecular processes that link comorbid traits such as addictions and mental disorders can provide novel therapeutic targets. Neuregulin signaling pathway (NSP) has previously been implicated in schizophrenia, a neurodevelopmental disorder with high comorbidity to smoking. Using a Finnish twin family sample, we have previously detected association between nicotine dependence and ERBB4 (a neuregulin receptor), and linkage for smoking initiation at the ERBB4 locus on 2q33. Further, Neuregulin3 has recently been shown to associate with nicotine withdrawal in a behavioral mouse model. In this study, we scrutinized association and linkage between 15 036 common, low frequency and rare genetic variants in 10 NSP genes and phenotypes encompassing smoking and alcohol use. Using the Finnish twin family sample (N=1998 from 740 families), we detected 66 variants (representing 23 LD blocks) significantly associated (false discovery rate P<0.05) with smoking initiation, nicotine dependence and nicotine withdrawal. We comprehensively annotated the associated variants using expression (eQTL) and methylation quantitative trait loci (meQTL) analyses in a Finnish population sample. Among the 66 variants, we identified 25 eQTLs (in NRG1 and ERBB4), 22 meQTLs (in NRG3, ERBB4 and PSENEN), a missense variant in NRG1 (rs113317778) and a splicing disruption variant in ERBB4 (rs13385826). Majority of the QTLs in blood were replicated in silico using publicly available databases, with additional QTLs observed in brain. In conclusion, our results support the involvement of NSP in smoking behavior but not in alcohol use and abuse, and disclose functional potential for 56 of the 66 associated single-nucleotide polymorphism.

Prospective association between tobacco smoking and death by suicide: a competing risks hazard analysis in a large twin cohort with 35-year follow-up

Background The relationship between smoking and suicide remains controversial. Method A total of 16 282 twin pairs born before 1958 in Finland and alive in 1974 were queried with detailed health and smoking questionnaires in 1975 and 1981, with response rates of 89% and 84%. Smoking status and dose, marital, employment, and socio-economic status, and indicators of psychiatric and somatic illness were assessed at both time points. Emergent psychiatric and medical illness and vital status, including suicide determined by forensic autopsy, were evaluated over 35-year follow-up through government registries. The association between smoking and suicide was determined in competing risks hazard models. In twin pairs discordant for smoking and suicide, the prospective association between smoking and suicide was determined using a matched case–control design. Results Smokers had a higher cumulative suicide incidence than former or never smokers. Heavy smokers had significantly higher suicide risk [hazard ratio (HR) 3.47, 95% confidence interval (CI) 2.31–5.22] than light smokers (HR 2.30, 95% CI 1.61–3.23) (p = 0.017). Compared with never smokers, smokers, but not former smokers, had increased suicide risk (HR 2.56, 95% CI 1.43–4.59), adjusting for depressive symptoms, alcohol and sedative–hypnotic use, and excluding those who developed serious somatic or psychiatric illness. In twin pairs discordant for smoking and suicide, suicide was more likely in smokers [odds ratio (OR) 6.0, 95% CI 2.06–23.8]. Conclusions Adults who smoked tobacco were more likely to die by suicide, with a large, dose-dependent effect. This effect remained after consideration of many known predictors of suicide and shared familial effects, consistent with the hypothesis that exposure to tobacco smoke increases the risk of suicide.

Prospective association between tobacco smoking and death by suicide

Background The relationship between smoking and suicide remains controversial. Method A total of 16 282 twin pairs born before 1958 in Finland and alive in 1974 were queried with detailed health and smoking questionnaires in 1975 and 1981, with response rates of 89% and 84%. Smoking status and dose, marital, employment, and socio-economic status, and indicators of psychiatric and somatic illness were assessed at both time points. Emergent psychiatric and medical illness and vital status, including suicide determined by forensic autopsy, were evaluated over 35-year follow-up through government registries. The association between smoking and suicide was determined in competing risks hazard models. In twin pairs discordant for smoking and suicide, the prospective association between smoking and suicide was determined using a matched case–control design. Results Smokers had a higher cumulative suicide incidence than former or never smokers. Heavy smokers had significantly higher suicide risk [hazard ratio (HR) 3.47, 95% confidence interval (CI) 2.31–5.22] than light smokers (HR 2.30, 95% CI 1.61–3.23) (p = 0.017). Compared with never smokers, smokers, but not former smokers, had increased suicide risk (HR 2.56, 95% CI 1.43–4.59), adjusting for depressive symptoms, alcohol and sedative–hypnotic use, and excluding those who developed serious somatic or psychiatric illness. In twin pairs discordant for smoking and suicide, suicide was more likely in smokers [odds ratio (OR) 6.0, 95% CI 2.06–23.8]. Conclusions Adults who smoked tobacco were more likely to die by suicide, with a large, dose-dependent effect. This effect remained after consideration of many known predictors of suicide and shared familial effects, consistent with the hypothesis that exposure to tobacco smoke increases the risk of suicide.

Persistent leisure-time physical activity in adulthood and use of antidepressants: A follow-up study among twins

BACKGROUND To study whether persistent leisure-time physical activity (PA) during adulthood predicts use of antidepressants later in life. METHODS The Finnish Twin Cohort comprises same-sex twin pairs born before 1958, of whom 11 325 individuals answered PA questions in 1975, 1981 and 1990 at a mean age of 44 years (range 33-60). PA volume over 15-years was used as the predictor of subsequent use of antidepressants. Antidepressant use (measured as number of purchases) for 1995-2004 were collected from the Finnish Social Insurance Institution (KELA) prescription register. Conditional logistic regression was conducted to calculate odds ratios (OR) with 95% confidence intervals (CI) for the use of antidepressants in pairs discordant for PA (642, including 164 monozygotic (MZ) pairs). RESULTS Altogether 229 persons had used at least one prescribed antidepressant during the study period. Active co-twins had a lower risk (unadjusted OR 0.80, 95%CI 0.67-0.95) for using any amount of antidepressants than their inactive co-twins; trends being similar for DZ (0.80, 0.67-0.97) and MZ pairs (0.78, 0.51-1.17). The lowest odds ratio (0.51, 0.26-0.98) was seen among MZ pairs after adjusting for BMI, smoking and binge drinking. The point estimates were similar but non-significant for long-term antidepressant use (4+purchases equivalent to 12 months use). LIMITATIONS Self-reported physical activity and low number of discordant MZ pairs. DISCUSSION Use of antidepressants was less common among physically active co-twins even when shared childhood experiences and genetic background were controlled for. Physical activity in midlife may therefore be important in preventing mild depression later in life.