Xiao-Ou Shu

Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P = 3.0 × 10(-14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P = 1.2 × 10(-7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P = 6.8 × 10(-165)), ADIPOQ (P = 1.8 × 10(-22)), PEPD (P = 3.6 × 10(-12)), CMIP (P = 2.1 × 10(-10)), ZNF664 (P = 2.3 × 10(-7)) and GPR109A (P = 7.4 × 10(-6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 × 10(-7)). We further confirmed the independence of two pairs of closely located loci (<2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P = 3.3 × 10(-4)), high density lipoprotein cholesterol (HDL-C, P = 4.9 × 10(-4)) and body mass index (BMI)-adjusted waist-hip ratio (P = 9.8 × 10(-3)). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.

Studies of the association between induced abortion and breast cancer risk have been inconsistent, perhaps due to underreporting of abortions. Induced abortion is a well-accepted family planning procedure in China, and women who have several induced abortions do not feel stigmatized. The authors used data from a population-based case-control study of breast cancer among women age 25-64 conducted between 1996 and 1998 in urban Shanghai to assess whether a history of and the number of induced abortions were related to breast cancer risk. In-person interviews were completed with 1,459 incident breast cancer cases ascertained through a population-based cancer registry, and 1,556 controls randomly selected from the general population in Shanghai (with respective response rates of 91% and 90%). After adjusting for confounding, there was no relation between ever having had an induced abortion and breast cancer (odds ratio [OR] = 0.9, 95% confidence interval [CI] 0.7-1.2). Women who had 3 or more induced abortions were not at increased risk of premenopausal breast cancer (OR = 0.9, 95% CI 0.6-1.4) or postmenopausal breast cancer (OR = 1.3, 95% CI 0.8-2.3). These results suggest that a history of several induced abortions has little influence on breast cancer risk in Chinese women.