Objectives/Goals: To identify population-specific and ancestry-informed genetic loci for blood pressure traits, characterize X chromosome associations, and evaluate evidence for evolutionary pressures influencing blood pressure risk across ancestries, which may be used downstream clinically for personalized medicine and drug target identification. Methods/Study Population: We conducted multi-ancestry and ancestry-stratified genome-wide association studies (GWAS) of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) across >2.5M individuals (40% non-European) from 16 cohorts and biobanks. Analyses were adjusted for age, age², sex, body mass index, and the first 10 principal components. Fixed-effects meta-analyses were followed by SuSiEx cross-population fine-mapping to identify ancestry-specific loci. We evaluated genetic differentiation using the fixation index (FST) and allele frequency directionality using the sign test to infer potential evolutionary pressures. Results/Anticipated Results: Multi-ancestry meta-analyses identified 2,406 significant independent loci for SBP (1,594 novel), 2,358 DBP (1,509 novel), and 2,312 PP (1,432 novel). Chromosome X analyses revealed 8 SBP, 80 DBP, and 8 PP loci. SuSiEx fine-mapping identified ancestry-specific signals, including a pulse pressure SNP near CTSL (Asian-specific) and a DBP SNP in CACNA1D (African-specific). Sign tests indicated enrichment of DBP risk alleles when comparing African and Asian populations and when comparing Admixed American and Asian populations (p < 0.01), supported by elevated FST values for variants with larger effect sizes. These findings suggest that ancestry-specific selection may influence blood pressure regulation. Discussion/Significance of Impact: This is the largest and most ancestrally diverse blood pressure genetics study to date and one of few to include X chromosome analyses, which enabled discovery of thousands of novel and population-specific loci and revealed evolutionary and biological insights that may advance precision medicine for hypertension.

Objectives/Goals: Identify genetic variants associated with the development of diabetic retinopathy (DR) and its advanced complication, diabetic macular edema (DME). Despite DME being a leading cause of vision loss among people with diabetes, genetic findings have been limited by small sample size, underrepresentation of diverse populations, and poor study design. Methods/Study Population: Genome-wide association studies (GWAS) were conducted to identify genetic variants linked to DME. GWAS were conducted separately by ancestry (African, European, and Admixed American) in the Million Veteran Program and All of Us cohorts, adjusted for age, sex, BMI, diabetes duration, mean HbA1c, and 10 principal components. We then combined population groups to perform a multi-ancestry meta-analysis (Multi) using a software called METAL. Analyses included autosomes and chromosome X for DME versus DR controls (14,211 cases and 47,005 controls). Gene expression analyses were performed using S-PrediXcan across 49 tissues to identify genes whose predicted expression is associated with DME risk. APOL1 variant and haplotype analyses were conducted to assess ancestry-specific associations with DME and type 2 diabetes. Results/Anticipated Results: Genome-wide significant loci included G6PD (Multi and African), previously reported to influence diabetes diagnosis, and APOL1 (Multi and European), previously linked to kidney disease in African ancestry. Gene expression analyses revealed 32 significant gene–tissue pairs (Multi 18 and African 18), corresponding to 9 unique genes. In APOL1, E150K was strongly associated with DME in Europeans (OR=1.22, P=2.9×10−8) and modestly in Africans (OR=1.18, P=5.3×10−4). N264K also showed significant effects in Europeans (OR=1.42, P=9.8×10−4) and weaker but consistent effects in Africans (OR=1.04, P=0.025). The high-risk G1/G2 haplotype demonstrated a modest association in African ancestry (OR=1.15, P=0.048). Discussion/Significance of Impact: This is the largest genetic study of DME, uncovering genetic risk factors that could potentially be driving risk, such as APOL1, a gene historically tied to kidney disease among individuals of African ancestry. Our results indicate its involvement may extend to diabetic complications more generally.

Comics are one of the paradigmatic forms of hybrid media, and coming up with a satisfactory definition for it has been difficult. Cowling, S. & Wesley D. C. (2022) take a functional approach and offer an Intentional Picture-Reading View which defines comics as something that is “aptly intended to be picture-read.” I show that the view is extensionally inadequate as is because formally ambitious prose and concrete poetry, too, are aptly intended to be picture-read. The way forward, I argue, is to look at more medium-specific non-depictive images (such as speech balloons and panels) to set comics apart from other hybrid media.

To observe the axial growth behavior of InAs on GaAs nanowires, InAs was grown for different growth durations on GaAs nanowires using Au nanoparticles. Through transmission electron microscopy, we have observed the following evolution steps for the InAs growth. (1) In the initial stages of the InAs growth, InAs cluster into a wedge shape preferentially at an edge of the Au/GaAs interface by minimizing Au/InAs interfacial area; (2) with further growth of InAs, the Au particles move sidewards and then downwards by preserving an interface with GaAs nanowire sidewalls. The lower interfacial energy of Au/GaAs than that of Au/InAs is attributed to be the reason for such Au movement. This downward movement of Au nanoparticle later terminates when the nanoparticle encounters InAs growing radially on the GaAs nanowire sidewalls, and with further supply of In and As vapor reactants, the Au nanoparticles assist the formation of InAs branches. These observations give some insights of vapor-liquid-solid growth and the kinks formation in nanowire heterostructures.