Several copy number variants have been associated with neuropsychiatric disorders and these variants have been shown to also influence cognitive abilities in carriers unaffected by psychiatric disorders. Previously, we associated the 15q11.2(BP1-BP2) deletion with specific learning disabilities and a larger corpus callosum. Here we investigate, in a much larger sample, the effect of the 15q11.2(BP1-BP2) deletion on cognitive, structural and functional correlates of dyslexia and dyscalculia. We report that the deletion confers greatest risk of the combined phenotype of dyslexia and dyscalculia. We also show that the deletion associates with a smaller left fusiform gyrus. Moreover, tailored functional magnetic resonance imaging experiments using phonological lexical decision and multiplication verification tasks demonstrate altered activation in the left fusiform and the left angular gyri in carriers. Thus, by using convergent evidence from neuropsychological testing, and structural and functional neuroimaging, we show that the 15q11.2(BP1-BP2) deletion affects cognitive, structural and functional correlates of both dyslexia and dyscalculia.
AIMS: To investigate whether length of employment as a cabin attendant was related to breast cancer risk, when adjusted for reproductive factors. METHODS: Age matched case-control study nested in a cohort of cabin attendants. The cases were found from a nationwide cancer registry (followed up to end of year 2000) and the reproductive factors (age at first childbirth and number of children) from a registry of childbirth, in both instances by record linkage with the cabin attendants' identification numbers. The employment time of the cabin attendants at the airline companies and the reproductive factors had been systematically recorded prior to the diagnosis of breast cancer in the cohort. A total of 35 breast cancer cases and 140 age matched controls selected from a cohort of 1532 female cabin attendants were included in the study. RESULTS: The matched odds ratio from conditional logistic regression of breast cancer risk among cases and controls of cabin attendants was 5.24 (95% CI 1.58 to 17.38) for those who had five or more years of employment before 1971 compared with those with less than five years of employment before 1971, adjusted for age at first childbirth and length of employment from 1971 or later. CONCLUSIONS: The association between length of employment and risk of breast cancer, adjusted for reproductive factors, indicates that occupational factors may be an important cause of breast cancer among cabin attendants; the association is compatible with a long induction period.
Comment In: Occup Environ Med. 2003 Nov;60(11):805-614573708
Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34,216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 ? 10(-7)). These findings replicate in a second large data set (N=127,274, thereof 76,242 smokers) for both SI (P=1.2 ? 10(-5)) and CPD (P=9.3 ? 10(-5)). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.
Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency=0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P=1.2 × 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P=4.0 × 10(-4)), chronic obstructive pulmonary disease (COPD; P=9.3 × 10(-4)), peripheral artery disease (PAD; P=0.090) and abdominal aortic aneurysms (AAAs; P=0.12), and the variant associates strongly with the early-onset forms of LC (OR=4.49, P=2.2 × 10(-4)), COPD (OR=3.22, P=2.9 × 10(-4)), PAD (OR=3.47, P=9.2 × 10(-3)) and AAA (OR=6.44, P=6.3 × 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P=6.8 × 10(-5)), particularly for early-onset cases (P=2.1 × 10(-7)). Our results are in agreement with functional studies showing that the human a4ß2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.