South Asians are at high risk of developing type 2 diabetes (T2D). We carried out a genome-wide association meta-analysis with South Asian T2D cases (n = 16,677) and controls (n = 33,856), followed by combined analyses with Europeans (n_eff = 231,420). We identify 21 novel genetic loci for significant association with T2D (P = 4.7 × 10⁻⁸ to 5.2 × 10⁻¹²), to the best of our knowledge at the point of analysis. The loci are enriched for regulatory features, including DNA methylation and gene expression in relevant tissues, and highlight CHMP4B, PDHB, LRIG1 and other genes linked to adiposity and glucose metabolism. A polygenic risk score based on South Asian-derived summary statistics shows ~4-fold higher risk for T2D between the top and bottom quartile. Our results provide further insights into the genetic mechanisms underlying T2D, and highlight the opportunities for discovery from joint analysis of data from across ancestral populations.

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n_DM = 178,691, n_noDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.

Objective: To determine whether women with a history of surgery for cervical intraepithelial neoplasia (CIN) are at an increased risk of subfertility, measured as a time to pregnancy of more than 12 months.Design: Case–control study.Setting: Iowa Health in Pregnancy Study (IHIPS), a population‐based case–control study of preterm and small‐for‐gestational‐age (SGA) live birth outcomes (from May 2002 through June 2005) in the USA.Sample: Women with an intended pregnancy and a history of either one prior cervical surgery (n = 152), colposcopy only (n = 151), or no prior cervical surgery or colposcopy (n = 1021).Methods: Cervical treatment history, pregnancy intention, time to pregnancy, and other variables were self‐reported by computer‐assisted telephone interviews. Odds ratios were calculated using logistic regression to estimate the risk of prolonged time to pregnancy among women with a history of cervical surgery or colposcopy alone, compared with untreated women (control group).Main outcome measure: Prolonged time to pregnancy (i.e. >1 year).Results: Prolonged time to pregnancy was most prevalent among treated women (16.4%), compared with untreated women (8.4%) and women with colposcopy only (8.6%) (P = 0.039). After adjusting for covariates, women with prior cervical surgery had a more than two‐fold higher risk of prolonged time to pregnancy compared with untreated women (aOR 2.09, 95% CI 1.26–3.46). In contrast, women with a history of colposcopy only had a risk equivalent to that found among untreated women (aOR 1.02, 95% CI 0.56–1.89).Conclusions: Women with a history of cervical treatment for CIN are at increased risk of subfertility, measured as a time to pregnancy of more than 12 months.