Anneli Pouta

Kari Stefansson and colleagues report genome-wide meta-analyses for association to smoking behaviors within the population cohorts of the ENGAGE consortium. They report three loci associated to cigarettes smoked per day. Smoking is a common risk factor for many diseases1. We conducted genome-wide association meta-analyses for the number of cigarettes smoked per day (CPD) in smokers (n = 31,266) and smoking initiation (n = 46,481) using samples from the ENGAGE Consortium. In a second stage, we tested selected SNPs with in silico replication in the Tobacco and Genetics (TAG) and Glaxo Smith Kline (Ox-GSK) consortia cohorts (n = 45,691 smokers) and assessed some of those in a third sample of European ancestry (n = 9,040). Variants in three genomic regions associated with CPD (P < 5 × 10−8), including previously identified SNPs at 15q25 represented by rs1051730[A] (effect size = 0.80 CPD, P = 2.4 × 10−69), and SNPs at 19q13 and 8p11, represented by rs4105144[C] (effect size = 0.39 CPD, P = 2.2 × 10−12) and rs6474412-T (effect size = 0.29 CPD, P = 1.4 × 10−8), respectively. Among the genes at the two newly associated loci are genes encoding nicotine-metabolizing enzymes (CYP2A6 and CYP2B6) and nicotinic acetylcholine receptor subunits (CHRNB3 and CHRNA6), all of which have been highlighted in previous studies of smoking and nicotine dependence2,3,4. Nominal associations with lung cancer were observed at both 8p11 (rs6474412[T], odds ratio (OR) = 1.09, P = 0.04) and 19q13 (rs4105144[C], OR = 1.12, P = 0.0006).

Objective. To determine whether Chlamydia pneumoniae antibodies and highly sensitive C-reactive protein (hsCRP) levels in maternal sera are associated with preeclampsia or gestational hypertension. Methods. C. pneumoniae antibodies and hsCRP levels were measured in maternal serum during first trimester (mean, 10.4 weeks of gestation) using the microimmunofluorescence (MIF) test and a highly sensitive immunoenzymometric assay, respectively. Results. No differences in the IgG antibody levels against C. pneumoniae or hsCRP levels were seen between the women with preeclampsia or gestational hypertension and those in the reference group. However, the women with preeclampsia and preterm delivery had serum IgG antibodies to C. pneumoniae (IgG titre ≥32) significantly more often in their first trimester sera compared with women having preeclampsia and full-term deliveries (p = 0.03). In addition, the proportion of subjects with C. pneumoniae IgG antibodies (IgG titre ≥32) and/or elevated CRP levels (≥3.8 mg/L, upper quartile) was double among the women with preeclampsia and elective preterm delivery compared with the women with preeclampsia who delivered at term (p = 0.01). Conclusion. Our results suggest that chronic C. pneumoniae infection and systemic low-grade inflammation may be associated with preeclampsia requiring elective delivery before 37 weeks gestation.

Objective: To find out whether there is an association between parity and mortality. Design: Prospective cohort study. Setting: Northern Finland, 1966–2001. Participants and methods: 12 055 women in the two northernmost provinces of Finland were followed up from pregnancy in 1966–2001, the coverage percentage being 96%. The data on age, smoking, body mass index, socioeconomic position, age at menarche and age at first birth were collected during pregnancy, and data on deaths were obtained from the National Cause of Death Statistics, maintained by Statistics Finland. The Cox proportional hazard model was used to estimate relative mortality between parity groups. Results: Total mortality was lowest among the women with 2–4 children (reference group). High parity was associated with an up to twofold risk of mortality from vascular complications, but after adjustment for all background factors, this significance disappeared. Mortality from haemorrhagic stroke was fourfold higher among the women with ⩾10 births compared with those of the reference group. No differences in cerebral infarction or total cancer mortality were seen between the groups. Primiparity was associated with increased mortality from accidental death (relative risk 2.6, 95% confidence interval 1.6 to 4.4). Conclusions: High parity was associated with an increased risk of mortality from vascular complications, especially haemorrhagic stroke, and primiparity with an increased risk of accidental death.