Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent patient populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

This is the first study to investigate the associations of IGF-1, IGF-2 and IGFBP-3 concentrations with the risk of colorectal cancer in prospectively collected blood samples from an Oriental population. Between 1986 and 1989 serum samples were collected at baseline from 18 244 men, aged 45–65 years, without a history of cancer and living in Shanghai, China. IGF-1, IGF-2 and IGFBP-3 were measured in the serum of 135 men who developed colorectal cancer over 12 years of follow-up and 661 control subjects drawn from the cohort, who were matched to the index cases by neighbourhood of residence, age, and year and month of sample collection. Serum IGF-1 was not associated with risk of colorectal cancer. IGF-2 and IGFBP-3, on the other hand, exhibited statistically significant, positive associations with colorectal cancer risk when cases were confined to those diagnosed within a relatively short time period after enrolment (within 8 years). After adjustment for body mass index, cigarette smoking and alcohol intake, men in the highest versus the lowest quintile of IGF-2 and IGFBP-3 showed odds ratios of 2.74 (95% Cl = 1.67–4.50; 2-sided P for trend = 0.0008) and 2.85 (95% Cl = 1.69–4.81; 2-sided P for trend = 0.01), respectively. Our data thus suggest that circulating IGF-2 and IGFBP-3 can serve as early indicators of impending colorectal cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com