Refractive error is the most common eye disorder worldwide, and a prominent cause of blindness. Myopia affects over 30% of Western populations, and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses including 37,382 individuals from 27 studies of European ancestry, and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in subjects of European ancestry, of which 8 were shared with Asians. Combined analysis revealed 8 additional loci. The new loci include genes with functions in neurotransmission (GRIA4), ion channels (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2, BMP2), and eye development (SIX6, PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for subjects with the highest genetic load. Our results, accumulated across independent multi-ethnic studies, considerably advance understanding of mechanisms involved in refractive error and myopia.

Professional guidelines dictate that disease severity is a key criterion for carrier screening. Expanded carrier screening, which tests for hundreds to thousands of mutations simultaneously, requires an objective, systematic means of describing a given disease's severity to build screening panels. We hypothesized that diseases with characteristics deemed to be of highest impact would likewise be rated as most severe, and diseases with characteristics of lower impact would be rated as less severe. We describe a pilot test of this hypothesis in which we surveyed 192 health care professionals to determine the impact of specific disease phenotypic characteristics on perceived severity, and asked the same group to rate the severity of selected inherited diseases. The results support the hypothesis: we identified four “Tiers” of disease characteristics (1–4). Based on these responses, we developed an algorithm that, based on the combination of characteristics normally seen in an affected individual, classifies the disease as Profound, Severe, Moderate, or Mild. This algorithm allows simple classification of disease severity that is replicable and not labor intensive.

Throughout its native range, the Yellowstone cutthroat trout (YCT), Oncorhynchus clarkii bouvieri, is declining dramatically in both abundance and distribution as a result of introgression with introduced rainbow trout (RBT), O. mykiss. We sampled over 1,200 trout from the South Fork of the Snake River (SFSR) watershed, in southeastern Idaho and western Wyoming, and measured the extent of introgression of RBT genes into native gene pools of YCT using seven species-specific, co-dominant nuclear genetic markers. We also used mitochondrial DNA (mtDNA) haplotype differences between the two parental trout species to determine the directionality of the hybridization. We found low levels of RBT introgression (only 7% of sampled individuals had one or more RBT alleles) into YCT gene pools, with the majority of hybrids (78%) occurring in mainstem localities of the SFSR and in lower elevation reaches of certain tributaries. Hybridization was bidirectional with respect to mtDNA haplotype, but the majority of hybrids (75%) had YCT maternal haplotypes, indicative of the greater proportion (90%) of YCT-genotypes in the SFSR watershed. The primary factor influencing the geographic distribution of RBT introgressed individuals was fluvial distance from localities of stocking origin. To a lesser extent, elevation, also influenced the distribution of hybrid genotypes, with several entire tributaries and all upper elevation reaches within tributaries harboring only YCT-genotypes. Important management implications of the study suggest targeting particular tributaries and upper reaches within tributaries for YCT protection and exclusion of RBT hybrid colonization.

As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, β = −0.16 mm per minor allele, Pmeta = 2.69×10−10). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) = 0.75, 95% CI: 0.68–0.84, Pmeta = 4.38×10−7) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.