SUMMARY Maize (Zea mays ssp. mays) was domesticated in southwestern Mexico ~9,000 years ago from its wild ancestor, teosinte (Zea mays ssp. parviglumis) [1]. From its centre of origin, maize experienced a rapid range expansion and spread over 90°of latitude in the Americas [2–4] which required a novel flowering time adaptation. ZEA CENTRORADIALIS 8 (ZCN8) is the maize florigen gene and has a central role in mediating flowering [5, 6]. Here, we show that ZCN8 underlies a major quantitative trait locus (qDTA8) for flowering time that was consistently detected in multiple maize-teosinte experimental populations. Through association analysis in a large diverse panel of maize inbred lines, we identified a single nucleotide polymorphism (SNP-1245) in the ZCN8 promoter that showed the strongest association with flowering time. SNP-1245 co-segregated with qDTA8 in maize-teosinte mapping populations. We demonstrate that SNP-1245 is associated with differential binding by the flowering activator ZmMADS1. SNP-1245 was a target of selection during early domestication which drove the pre-existing early-flowering allele to near fixation in maize. Interestingly, we detected an independent association block upstream of SNP-1245, wherein the early-flowering allele that most likely originated from Zea mays ssp. mexicana introgressed into the early-flowering haplotype of SNP-1245 and contributed to maize adaptation to northern high latitudes. Our study demonstrates how independent cis-regulatory variants at a gene can be selected at different evolutionary times for local adaptation, highlighting how complex cis-regulatory control mechanisms evolve. Finally, we propose a polygenic map for the pre-Columbian spread of maize throughout the Americas.

Background Sex differences in the management of cardiovascular disease have been reported in secondary care. We conducted a systematic review with meta‐analysis of systematically investigated sex differences in cardiovascular medication prescription among patients at high risk or with established cardiovascular disease in primary care. Methods and Results PubMed and Embase were searched between 2000 and 2019 for observational studies reporting on the sex‐specific prevalence of aspirin, statins, and antihypertensive medication prescription, including beta blockers, calcium channel blockers, angiotensin‐converting enzyme inhibitors, and diuretics, in primary care. Random effects meta‐analysis was used to obtain pooled women‐to‐men prevalence ratios for each cardiovascular medication prescription. Metaregression models assessed the impact of age and year on the findings. A total of 43 studies were included, involving 2 264 600 participants (28% women) worldwide. Participants’ mean age ranged from 51 to 76 years. The pooled prevalence of cardiovascular medication prescription for women was 41% for aspirin, 60% for statins, and 68% for any antihypertensive medications. Corresponding rates for men were 56%, 63%, and 69% respectively. The pooled women‐to‐men prevalence ratios were 0.81 (95% CI , 0.72–0.92) for aspirin, 0.90 (95% CI , 0.85–0.95) for statins, and 1.01 (95% CI , 0.95–1.08) for any antihypertensive medications. Women were less likely to be prescribed angiotensin‐converting enzyme inhibitors (0.85; 95% CI , 0.81–0.89) but more likely with diuretics (1.27; 95% CI , 1.17–1.37). Mean age, mean age difference between the sexes, and year of study had no significant impact on findings. Conclusions Sex differences in the prescription of cardiovascular medication exist among patients at high risk or with established cardiovascular disease in primary care, with a lower prevalence of aspirin, statins, and angiotensin‐converting enzyme inhibitors prescription in women and a lower prevalence of diuretics prescription in men.

ObjectiveTo investigate whether there are sex differences in risk factor management of patients with established coronary heart disease (CHD), and to assess demographic variations of any potential sex differences.MethodsPatients with CHD were recruited from Europe, Asia, and the Middle East between 2012-2013. Adherence to guideline-recommended treatment and lifestyle targets was assessed and summarised as a Cardiovascular Health Index Score (CHIS). Age-adjusted regression models were used to estimate odds ratios for women versus men in risk factor management.Results10 112 patients (29% women) were included. Compared with men, women were less likely to achieve targets for total cholesterol (OR 0.50, 95% CI 0.43 to 0.59), low-density lipoprotein cholesterol (OR 0.57, 95% CI 0.51 to 0.64), and glucose (OR 0.78, 95% CI 0.70 to 0.87), or to be physically active (OR 0.74, 95% CI 0.68 to 0.81) or non-obese (OR 0.82, 95% CI 0.74 to 0.90). In contrast, women had better control of blood pressure (OR 1.31, 95% CI 1.20 to 1.44) and were more likely to be a non-smoker (OR 1.93, 95% CI 1.67 to 2.22) than men. Overall, women were less likely than men to achieve all treatment targets (OR 0.75, 95% CI 0.60 to 0.93) or obtain an adequate CHIS (OR 0.81, 95% CI 0.73 to 0.91), but no significant differences were found for all lifestyle targets (OR 0.93, 95% CI 0.84 to 1.02). Sex disparities in reaching treatment targets were smaller in Europe than in Asia and the Middle East. Women in Asia were more likely than men to reach lifestyle targets, with opposing results in Europe and the Middle East.ConclusionsRisk factor management for the secondary prevention of CHD was generally worse in women than in men. The magnitude and direction of the sex differences varied by region.

SURF proved to be practical in daily practice. Results indicated poor control of risk factors with substantial variation between countries, calling for development and implementation of clinical standards of secondary prevention of coronary heart disease.