Background
Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes.

/pdf/genome-wide-association-study-of-retinopathy-in-individuals-5buwyfgl9i.pdf

Genome-Wide Association Study of Retinopathy in Individuals Without Diabetes

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry We identified 19 loci associated at P < 5 × 10(-8) These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis Our results include seven loci with associations reaching P < 5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined Our findings provide new directions for biological, genetic and therapeutic studies of AMD

/pdf/seven-new-loci-associated-with-age-related-macular-2pcj8omqcw.pdf

Seven new loci associated with age-related macular degeneration

Tyrosine kinase inhibitors (TKIs) elicit high response rates among individuals with kinase-driven malignancies, including chronic myeloid leukemia (CML) and epidermal growth factor receptor-mutated non-small-cell lung cancer (EGFR NSCLC). However, the extent and duration of these responses are heterogeneous, suggesting the existence of genetic modifiers affecting an individual's response to TKIs. Using paired-end DNA sequencing, we discovered a common intronic deletion polymorphism in the gene encoding BCL2-like 11 (BIM). BIM is a pro-apoptotic member of the B-cell CLL/lymphoma 2 (BCL2) family of proteins, and its upregulation is required for TKIs to induce apoptosis in kinase-driven cancers. The polymorphism switched BIM splicing from exon 4 to exon 3, which resulted in expression of BIM isoforms lacking the pro-apoptotic BCL2-homology domain 3 (BH3). The polymorphism was sufficient to confer intrinsic TKI resistance in CML and EGFR NSCLC cell lines, but this resistance could be overcome with BH3-mimetic drugs. Notably, individuals with CML and EGFR NSCLC harboring the polymorphism experienced significantly inferior responses to TKIs than did individuals without the polymorphism (P = 0.02 for CML and P = 0.027 for EGFR NSCLC). Our results offer an explanation for the heterogeneity of TKI responses across individuals and suggest the possibility of personalizing therapy with BH3 mimetics to overcome BIM-polymorphism-associated TKI resistance.

A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer.

John Chambers and colleagues report a genome-wide association study for type 2 diabetes in individuals of south Asian ancestry. They identify six loci newly associated with type 2 diabetes.

/pdf/genome-wide-association-study-in-individuals-of-south-asian-4ezybr27we.pdf

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

Lens Vault, Thickness, and Position in Chinese Subjects with Angle Closure

Purpose: Current knowledge of ethnic variability in the epidemiology of major eye diseases in Asia is limited. This report summarizes the rationale and study design of the Singapore Indian Chinese Cohort (SICC) Eye Study, a population-based study of ethnic South Asian (Indians) and East Asian (Chinese) older adults in Singapore.Methods: The SICC examined a population-based cross-sectional sample of 3,300 ethnic Indians and 3,300 ethnic Chinese aged 40–80+ years residing in the South-Western part of Singapore. Results: From two lists of 12,000 names of each ethnic group provided by the Ministry of Home Affairs, age-stratified random sampling was used to select 6,350 names in each group, with a target sample size of 3,300. Invitations were sent to attend a central clinic using letters, telephone calls and home visits. Examination procedures included interviews, measurement of blood pressure, anthropometry, presenting and best-corrected visual acuity, subjective refraction, ocular biometry, Goldmann applanat...

Vse Jeganathan

Papers

Methodology of the Singapore Indian Chinese Cohort (SICC) Eye Study: Quantifying ethnic variations in the epidemiology of eye diseases in Asians