Multi-ancestry polygenic risk scores for venous thromboembolism.

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality, with large disparities in incidence rates between Black and White Americans. Polygenic risk scores (PRSs) limited to variants discovered in genome-wide association studies in European-ancestry samples can identify European-ancestry individuals at high risk of VTE. However, there is limited evidence on whether high-dimensional PRS constructed using more sophisticated methods and more diverse training data can enhance the predictive ability and their utility across diverse populations. We developed PRSs for VTE using summary statistics from the International Network against Venous Thrombosis (INVENT) consortium genome-wide association studies meta-analyses of European- (71 771 cases and 1 059 740 controls) and African-ancestry samples (7482 cases and 129 975 controls). We used LDpred2 and PRS-CSx to construct ancestry-specific and multi-ancestry PRSs and evaluated their performance in an independent European- (6781 cases and 103 016 controls) and African-ancestry sample (1385 cases and 12 569 controls). Multi-ancestry PRSs with weights tuned in European-ancestry samples slightly outperformed ancestry-specific PRSs in European-ancestry test samples (e.g. the area under the receiver operating curve [AUC] was 0.609 for PRS-CSx_combinedEUR and 0.608 for PRS-CSxEUR [P = 0.00029]). Multi-ancestry PRSs with weights tuned in African-ancestry samples also outperformed ancestry-specific PRSs in African-ancestry test samples (PRS-CSxAFR: AUC = 0.58, PRS-CSx_combined AFR: AUC = 0.59), although this difference was not statistically significant (P = 0.34). The highest fifth percentile of the best-performing PRS was associated with 1.9-fold and 1.68-fold increased risk for VTE among European- and African-ancestry subjects, respectively, relative to those in the middle stratum. These findings suggest that the multi-ancestry PRS might be used to improve performance across diverse populations to identify individuals at highest risk for VTE.

Multi-ancestry polygenic risk scores for venous thromboembolism.

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality, with large disparities in incidence rates between Black and White Americans. Polygenic risk scores (PRSs) limited to variants discovered in genome-wide association studies in European-ancestry samples can identify European-ancestry individuals at high risk of VTE. However, there is limited evidence on whether high-dimensional PRS constructed using more sophisticated methods and more diverse training data can enhance the predictive ability and their utility across diverse populations. We developed PRSs for VTE using summary statistics from the International Network against Venous Thrombosis (INVENT) consortium GWAS meta-analyses of European- (71,771 cases and 1,059,740 controls) and African-ancestry samples (7,482 cases and 129,975 controls). We used LDpred2 and PRSCSx to construct ancestry-specific and multi-ancestry PRSs and evaluated their performance in an independent European- (6,261 cases and 88,238 controls) and African-ancestry sample (1,385 cases and 12,569 controls). Multi-ancestry PRSs with weights tuned in European- and African-ancestry samples, respectively, outperformed ancestry-specific PRSs in European- (PRSCSXEUR: AUC=0.61 (0.60, 0.61), PRSCSX_combinedEUR: AUC=0.61 (0.60, 0.62)) and African-ancestry test samples (PRSCSXAFR: AUC=0.58 (0.57, 0.6), PRSCSX_combined AFR: AUC=0.59 (0.57, 0.60)). The highest fifth percentile of the best-performing PRS was associated with 1.9-fold and 1.68-fold increased risk for VTE among European- and African-ancestry subjects, respectively, relative to those in the middle stratum. These findings suggest that the multi-ancestry PRS may be used to identify individuals at highest risk for VTE and provide guidance for the most effective treatment strategy across diverse populations.

Discrimination of Odors Associated With Conspecific and Heterospecific Frass by Sibling Species Dendroctonus frontalis (Coleoptera: Curculionidae: Scolytinae) and Dendroctonus mesoamericanus (Coleoptera: Curculionidae: Scolytinae).

In the Central American region, the aggressive, sibling bark beetles Dendroctonus frontalis Zimmermann (Coleoptera: Curculionidae: Scolytinae) and Dendroctonus mesoamericanus Armendáriz-Toledano & Sullivan (Coleoptera: Curculionidae: Scolytinae) commonly colonize pines concurrently, and in nature they avoid heterospecific pairing, although it can be produced in the lab. We performed walking arrestment bioassays in the lab to examine the capacity of both sexes of both species to discriminate odors from frass expelled from gallery entrances of either solitary females or conspecific pairs of either species. Males of both species strongly preferred odors of frass from solitary, conspecific females over those of heterospecific females or pairs of either species. Female D. frontalis did not discriminate among these frass categories, whereas female D. mesoamericanus preferred frass of conspecific females. In gas chromatography-electroantennographic detection and gas chromatography-mass spectrometry analyses, we determined that males of both species could sense a nearly identical spectrum of approximately 16 host- and beetle-produced compounds present in frass of females of one or both species. Only two of these compounds, endo-brevicomin and ipsdienol, which were present in frass of female D. mesoamericanus and pairs of either species but absent in frass of solitary D. frontalis females, qualitatively distinguished these categories. Several known attractants and synergists for either species declined in concentration postpairing. Our results complement earlier research and indicate how semiochemical composition and concentration in frass might mediate male discrimination of attack sites of conspecific, unpaired females. Furthermore, our data indicate that semiochemical responses for walking females differ from those of males and between species.

Responses by Dendroctonus frontalis and Dendroctonus mesoamericanus (Coleoptera: Curculionidae) to Semiochemical Lures in Chiapas, Mexico: Possible Roles of Pheromones During Joint Host Attacks.

In southern Mexico and Central America, the southern pine beetle Dendroctonus frontalis Zimmermann (Coleoptera: Curculionidae: Scolytinae) commonly colonizes host trees simultaneously with Dendroctonus mesoamericanus Armendáriz-Toledano and Sullivan, a recently described sibling species. We hypothesized that cross-species pheromone responses by host-seeking beetles might mediate joint mass attack, bole partitioning, and reproductive isolation between the species. Previous studies had indicated that D. frontalis females produce frontalin and that female D. mesoamericanus produce frontalin, endo-brevicomin, and ipsdienol (males of both species produce endo-brevicomin and possibly ipsdienol). In field trapping trials in the Mexican state of Chiapas, D. frontalis was attracted to the lure combination of turpentine and racemic frontalin; racemic endo-brevicomin enhanced this response. In a single test, D. mesoamericanus was attracted in low numbers to the combination of turpentine, racemic frontalin, and racemic endo-brevicomin after the addition of racemic ipsdienol; in contrast, racemic ipsdienol reduced responses of D. frontalis. Inhibition of D. frontalis was generated in both sexes by (+)- and racemic ipsdienol, but by (−)-ipsdienol only in females. Logs infested with D. mesoamericanus females (the pioneer sex in Dendroctonus) attracted both species in greater numbers than either D. frontalis female-infested or uninfested logs. Our data imply that D. frontalis may be more attracted to pioneer attacks of D. mesoamericanus females, and that this could be owing to the presence of endo-brevicomin in the latter. Possible intra- and inter-specific functions of semiochemicals investigated in our experiments are discussed.

Pheromone-Mediated Mate Location and Discrimination by Two Syntopic Sibling Species of Dendroctonus Bark Beetles in Chiapas, Mexico.

Where their geographic and host ranges overlap, sibling species of tree-killing bark beetles may simultaneously attack and reproduce on the same hosts. However, sustainability of these potentially mutually beneficial associations demands effective prezygotic reproductive isolation mechanisms between the interacting species. The pine bark beetle, Dendroctonus frontalis Zimmermann, is syntopic in the Central American region with a recently described sibling species, Dendroctonus mesoamericanus Armendáriz-Toledano and Sullivan, but mechanisms for their reproductive isolation are uncertain. We investigated whether semiochemicals mediate species discrimination by mate-seeking males of both species. In olfactometer bioassays, walking males of both species strongly preferred odors from gallery entrances of conspecific females. Coupled gas chromatography-electroantennographic detection and gas chromatography-mass spectrometry isolated 16 olfactory stimulants for males in these odors, but only two, ipsdienol and endo-brevicomin (both from D. mesoamericanus females), differed in quantity in female-associated odors between the species. In olfactometer bioassays, with 10, 1, or 0.1 female entrance equivalents of synthetic semiochemicals, the combination of ipsdienol and endo-brevicomin inhibited responses of male D. frontalis and enhanced responses of male D. mesoamericanus to two compounds associated with female entrances of both species (the pheromone component frontalin and host odor α-pinene). We conclude that ipsdienol and endo-brevicomin, pheromone components produced by females of just one of the two species (D. mesoamericanus), mediate interspecific mate discrimination by males of both species and provide an apparently symmetrical reproductive isolation mechanism.

[Folic acid for neural tube defects prevention: consumption and information in fertil-age women in Centro Cuyo Region]. / Acido fólico para prevenir defectos del tubo neural: consumo e información en mujeres en edad fértil de la Región Centro Cuyo.

INTRODUCTION: Neural tube defects are congenital malformations of brain and spinal cord. There is evidence that adequate amounts of folic acid supply to women before and during early pregnancy decreases the risk of having a neural tube defects affected child. Main sources of folic acid are food rich in folic acid, multivitamins with folic acid supplementation, and folic acid fortification of cereal products. OBJECTIVES: To assess folic acid consumption from food and from medication in a group of mothers. To analyze their knowledge about using folic acid to prevent neural tube defects. To evaluate association between inadequate consumption and information, level of education, and concurrence to private or public health sector. To measure the amount of folic acid in bread sold within the region. DESIGN: Observational cross-sectional study. SURVEYS: Mothers of children under 2 months of age that were assisted by 38 pediatricians in five cities in the Region, collected between November 2006 and March 2007. Amount of folic acid in bread: bread samples acquired in the same cities. RESULTS AND CONCLUSIONS: 327 surveys were collected. The average daily intake of folic acid from food was 481 Hg; 43,4% of women consume less than 400 Hg daily. Medical supplementation was suitable in 27,8% of the sample. 52,9% had appropriated knowledge about folic acid and prevention of neural tube defects. Differences were observed between mothers concurring to private or public health sector, and those who had or had not completed secondary school in relation to both supplementation and knowledge of folic acid. The media amount of folic acid in bread samples was 192,34 Hg / 100 g. All samples were manufactured with fortified flour.