Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8×10−5), establishing a novel phenotype for this genetic variant

Economic Yield and Profitability of Maize/Melon Intercrop as Influenced by Inorganic Fertilizer Application in Humid Forest Ultisol

The trial assessed the viability and profitability of maize and melon production under sole and mixed cropping system on a forest Ultisol. This was conducted as an on-farm trial at Evboneka, Edo State, Nigeria in April 2008 and 2009. The trial involved three cropping patterns (sole maize, sole melon and maize/melon mixture) and four levels of NPK fertilizer (0, 200, 400 and 600 kg ha-1) in a 3 � 4 factorial arrangement in randomized complete block design with three replications. The results revealed that economic yield of maize and melon increased as the fertilizer rate increase. The sole crops had higher yield than in their mixed stands in the entire fertilizer rate. However, land equivalent ratio (LER) values of the mixed crop stands were higher than in their respective sole cropping. The LER was highest (1.47) in maize/melon mixed stands treated with 400 kg NPK ha-1. The production cost and economic return followed the same trend as they increased with an increase in fertilizer rate. The sole melon crop had the lowest production cost ($316.50-588.51) and economic return ($ 873-1,305) in the entire fertilizer rate compared to the sole maize and maize/melon mixed crop in that order. The net farm income does not follow a definite trend among the three cropping patterns, but the maize/melon intercrop value ($ 748.11-997.52) was the highest. The optimum yield was produced from maize/melon mixed stands treated with 200 kg ha-1. This treatment also gave the highest benefit-cost ratio of 2.19, in addition to ensuring better crop diversity in the rainforest ultisol

GROWTH AND HERBAGE YIELD OF Celosia argentea AS INFLUENCED BY PLANT DENSITY AND NPK FERTILIZATION IN DEGRADED ULTISOL

The effect of five plant densities (8,0000, 160,000, 250,000, 444,444 and 1,000,000 plants ha-1) and three levels of fertilizer (0, 200 and 400 kg NPK ha-1) on growth and yield of Celosia argentea was evaluated on degraded ultisol at Evboneka, Edo State, Nigeria in 2005 and 2006 cropping seasons. The trial was a 5 x 3 factorial arrangement fitted into a randomized complete block design in three replicates. Results revealed that plant density and fertilizer application affected significantly (P < 0.05) affected the plant height, stem girth, number of leaves, leaf area index and total dry weight leading to higher herbage yield. The plants grown under high plant density and fertilizer application level had higher degree of foliation and total dry weight than plants grown under lower plant density and fertilizer application levels. The greatest yield (13.67 tonnes hectare) was produced from a population of 444,444 plants with 400kg fertilizer rate. The production cost increased from $79.570 –$ 790.18, revenue from $1,008.00 –$ 2,460.60, gross margin from $948.08 –$ 2151.00, net income from $928.43 –$ 2,072.92 and benefit-cost ratio from 1.34 – 14.55 for the various treatment combinations. The best herbage yield was a population of 80,000 plants with 400 kg fertilizer rate based on the fact that it had the greatest benefit-cost ratio (14.55)

A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels

Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10−9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro

A genetic association study of circulating coagulation Factor VIII and von Willebrand Factor levels

Coagulation Factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single variant meta-analysis including up to 45,289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified three candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells (HUVECs). Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P&lt;5×10-9) at seven new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and one for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multi-phenotype analysis of FVIII and VWF identified another three new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, while silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and one for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

Abstract Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids