Comparison of prognosis in unrecognized versus recognized myocardial infarction in men versus women >55 years of age (from the Rotterdam Study).

Unrecognized myocardial infarction (MI) is frequent in the general population. Its prognosis is reported to be at least as unpropitious as that of recognized MI, particularly in men. However, contemporary data with long follow-up are lacking. The aims of this study were to investigate the long-term prognosis of unrecognized MI with respect to all-cause and cause-specific mortality and to investigate possible differences in prognosis by gender. In the population-based Rotterdam Study (2,672 men and 3,862 women), the presence of unrecognized MI and recognized MI was determined at baseline (1990 to 1993). The cohort was followed for nearly 2 decades for all-cause and cause-specific mortality. During 82,268 patient-years of follow-up (median 15.6 years) 3,412 patients died (1,300 from cardiovascular causes). Men and women with recognized and unrecognized MIs had increased total mortality rates compared with those without MIs. Hazard ratios (HRs) for men and women were 1.57 (95% confidence interval [CI] 1.36 to 1.81) and 1.89 (95% CI 1.56 to 2.30) for recognized MI and 1.72 (95% CI 1.43 to 2.07) and 1.36 (95% CI 1.14 to 1.61) for unrecognized MI. Unrecognized MI was associated with increased risks for cardiovascular mortality (men: HR 2.19, 95% CI 1.66 to 2.91; women: HR 1.36, 95% CI 1.03 to 1.81) and noncardiovascular mortality (men: HR 1.47, 95% CI 1.14 to 1.89; women: HR 1.39, 95% CI 1.10 to 1.75). In conclusion, the long-term prognosis of patients with unrecognized MIs is worse compared with those without MIs and applies not only to cardiovascular mortality but also to noncardiovascular mortality. In men, the prognosis is as unfavorable as that of patients with recognized MIs.

A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25.

Myopia and hyperopia are at opposite ends of the continuum of refraction, the measure of the eye's ability to focus light, which is an important cause of visual impairment (when aberrant) and is a highly heritable trait. We conducted a genome-wide association study for refractive error in 4,270 individuals from the TwinsUK cohort. We identified SNPs on 15q25 associated with refractive error (rs8027411, P = 7.91 × 10⁻8). We replicated this association in six adult cohorts of European ancestry with a combined 13,414 individuals (combined P = 2.07 × 10⁻9). This locus overlaps the transcription initiation site of RASGRF1, which is highly expressed in neurons and retina and has previously been implicated in retinal function and memory consolidation. Rasgrf1(-/-) mice show a heavier average crystalline lens (P = 0.001). The identification of a susceptibility locus for refractive error on 15q25 will be important in characterizing the molecular mechanism responsible for the most common cause of visual impairment.

A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14.

Refractive errors are the most common ocular disorders worldwide and may lead to blindness. Although this trait is highly heritable, identification of susceptibility genes has been challenging. We conducted a genome-wide association study for refractive error in 5,328 individuals from a Dutch population-based study with replication in four independent cohorts (combined 10,280 individuals in the replication stage). We identified a significant association at chromosome 15q14 (rs634990, P = 2.21 × 10⁻¹4). The odds ratio of myopia compared to hyperopia for the minor allele (minor allele frequency = 0.47) was 1.41 (95% CI 1.16-1.70) for individuals heterozygous for the allele and 1.83 (95% CI 1.42-2.36) for individuals homozygous for the allele. The associated locus is near two genes that are expressed in the retina, GJD2 and ACTC1, and appears to harbor regulatory elements which may influence transcription of these genes. Our data suggest that common variants at 15q14 influence susceptibility for refractive errors in the general population.