Individuals with monogenic disorders can experience variable phenotypes that are influenced by genetic variation. To investigate this in sickle cell disease (SCD), we performed whole-genome sequencing (WGS) of 722 individuals with hemoglobin HbSS or HbSβ0-thalassemia from Baylor College of Medicine and from the St. Jude Children’s Research Hospital Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort study. We developed pipelines to identify genetic variants that modulate sickle hemoglobin polymerization in red blood cells and combined these with pain-associated variants to build a polygenic score (PGS) for acute vaso-occlusive pain (VOP). Overall, we interrogated the α-thalassemia deletion −α3.7 and 133 candidate single-nucleotide polymorphisms (SNPs) across 66 genes for associations with VOP in 327 SCCRIP participants followed longitudinally over 6 years. Twenty-one SNPs in 9 loci were associated with VOP, including 3 (BCL11A, MYB, and the β-like globin gene cluster) that regulate erythrocyte fetal hemoglobin (HbF) levels and 6 (COMT, TBC1D1, KCNJ6, FAAH, NR3C1, and IL1A) that were associated previously with various pain syndromes. An unweighted PGS integrating all 21 SNPs was associated with the VOP event rate (estimate, 0.35; standard error, 0.04; P = 5.9 × 10−14) and VOP event occurrence (estimate, 0.42; standard error, 0.06; P = 4.1 × 10−13). These associations were stronger than those of any single locus. Our findings provide insights into the genetic modulation of VOP in children with SCD. More generally, we demonstrate the utility of WGS for investigating genetic contributions to the variable expression of SCD-associated morbidities.

No abstract

Abstract. Eurasian watermilfoil (Myriophyllum spicatum) is a non-native and invasive aquatic macrophyte with a broad North American distribution. It can have significant negative effects on invaded waterbodies, including decreased native macrophyte diversity, formation of recreational nuisances, and lowered lakefront property values. Previous research suggests that M. spicatum decreases in response to herbicide treatment, but most studies are spatially and temporally limited, usually focusing on a single waterbody for a single year. The long-term effects of herbicides remain relatively unknown. Here, we share the results of an 11-yr observational study of aquatic macrophyte diversity, dynamics, and response to herbicide treatment on 28 Wisconsin lakes (15 of which were adaptively managed with herbicide for M. spicatum and 13 of which acted as unmanaged reference lakes). We found that overall, adaptive management decreases M. spicatum abundance over time, but that the efficacy of individual herbicide treatments can vary. We also found that lakes with relatively new M. spicatum populations (discovered within the last decade) treated smaller areas with lower frequency than lakes with established populations, and were able to maintain lower M. spicatum abundance. This suggests that using adaptive, science-based aquatic plant management strategies, including early detection and response, may increase invasive species management success. Finally, we show that the effect of herbicide treatment on native macrophytes is variable and can be significant. Overall, our results suggest that while herbicide treatment can be an effective adaptive management tool, particularly in lakes with relatively recent M. spicatum invasions, the specific effects of individual treatments can be unpredictable. This study allows lake stakeholders to better understand the efficacy of herbicide treatment, in addition to the possible non-target effects on native macrophyte species.

No abstract