Suggestive evidence for association between L‐type voltage‐gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family‐based association study

Objectives: Through recent genome‐wide association studies (GWASs), several groups have reported significant association between variants in the calcium channel, voltage‐dependent, L‐type, alpha 1C subunit (CACNA1C) and bipolar disorder (BP) in European and European‐American cohorts. We performed a family‐based association study to determine whether CACNA1C is associated with BP in the Latino population. Methods: This study included 913 individuals from 215 Latino pedigrees recruited from the USA, Mexico, Guatemala, and Costa Rica. The Illumina GoldenGate Genotyping Assay was used to genotype 58 single‐nucleotide polymorphisms (SNPs) that spanned a 602.9‐kb region encompassing the CACNA1C gene including two SNPs (rs7297582 and rs1006737) previously shown to associate with BP. Individual SNP and haplotype association analyses were performed using Family‐Based Association Test (version 2.0.3) and Haploview (version 4.2) software. Results: An eight‐locus haplotype block that included these two markers showed significant association with BP (global marker permuted p = 0.0018) in the Latino population. For individual SNPs, this sample had insufficient power (10%) to detect associations with SNPs with minor effect (odds ratio = 1.15). Conclusions: Although we were not able to replicate findings of association between individual CACNA1C SNPs rs7297582 and rs1006737 and BP, we were able to replicate the GWAS signal reported for CACNA1C through a haplotype analysis that encompassed these previously reported significant SNPs. These results provide additional evidence that CACNA1C is associated with BP and provides the first evidence that variations in this gene might play a role in the pathogenesis of this disorder in the Latino population.     

Association between granzyme B and perforin I polymorphisms and allograft outcomes in Hispanic kidney transplant recipients

Granzyme B (GZMB) and perforin 1 gene (PRF1) are key effector molecules of cytotoxic T lymphocytes, in causing acute and chronic solid organ transplant rejection. In this study, we analyzed the impact of GZMB and PRF1 polymorphism on kidney allograft outcomes. In all, 527 de novo kidney Hispanic allograft recipients were genotyped for PRF1 (rs10999426, rs35947132) and GZMB (rs8192917, rs7144366). PRF1 (rs10999426, rs35947132) G alleles and GG genotypes were negatively associated with allograft rejection, demonstrating protection against allograft rejection (OR = 0.61, p = 0.005 for rs1099946; OR = 0.4, p = 0.01 for rs 35947132). On the other hand, the GA heterozygosity of PRF1 was found marginally associated with the rejection group (OR = 1.53, p = 0.05 for rs10999426; OR = 2.24, p = 0.07 for rs35947132). There was a significant increase in allograft survival in time period studied for the PRF1 (rs10999426) GG genotype, while the GA heterozygosity was associated with graft failure. We found no association for polymorphic markers in GZMB gene with allograft rejection. Survival was significantly improved for patients who were homozygous TT for the GZMB (rs8192917) (TT vs. CC/TT, p = 0.041). The result suggests that PRF1 and GZMB gene polymorphisms may determine the incidence of acute rejection or graft survival among Hispanic allograft recipients.     

Early childhood caries screening tools: a comparison of four approaches

BackgroundEarly childhood caries (ECC) is prevalent and consequential. Risk assessment tools have been proposed that can be used to identify children who require intensive interventions. In this study, the authors compare four approaches for identifying children needing early and intensive intervention to prevent or minimize caries experience for their accuracy and clinical usefulness.MethodsThe authors screened 229 predominantly low-income Hispanic children younger than 3 years with ECC and 242 without ECC by using the American Academy of Pediatric Dentistry's Caries-risk Assessment Tool (CAT) and the optional screening measure of culturing Streptococcus mutans. The authors compared four approaches (CAT, CAT minus socioeconomic status, CAT minus socioeconomic status plus mutans streptococci [MS] and MS alone) for accuracy and clinical usefulness.ResultsThe results of the CAT demonstrated high sensitivity (100.0 percent) and negative predictive value (NPV) (100.0 percent) but low specificity (2.9 percent) and positive predictive value (PPV) (49.4 percent). The MS culture alone had the highest combination of accuracy and clinical usefulness (sensitivity, 86.5 percent; specificity, 93.4 percent; PPV, 92.5 percent; NPV, 87.9 percent). When we removed the socioeconomic status element, the CAT's performance improved.ConclusionsSalivary culture of MS alone in a population of young, low-income Hispanic childrenoutperformed the CAT and variations on the CAT for test accuracy (sensitivity and specificity) and clinical usefulness (predictive values).Clinical ImplicationsScreening for ECC by using salivary MS cultures and variations on the CAT are promising approaches for identifying children who need early and intensive intervention to prevent or minimize caries experience.     

A pilot study of Trabajadora de salud,a lay health worker intervention for Latinas/os with traumatic brain injuries and their caregivers

Background

Latinas/os with traumatic brain injuries (TBIs) and their caregivers experience worse outcomes than others.

Lessons Learned From a Feasibility Study Delivered in 2 WIC Sites to Promote Physical Activity Among Pregnant Latinas

Objective

To assess the feasibility, including demand for and acceptability of a physical activity (PA) intervention among pregnant Latinas recruited at the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

Properties of global‐ and local‐ancestry adjustments in genetic association tests in admixed populations

Population substructure can lead to confounding in tests for genetic association, and failure to adjust properly can result in spurious findings. Here we address this issue of confounding by considering the impact of global ancestry (average ancestry across the genome) and local ancestry (ancestry at a specific chromosomal location) on regression parameters and relative power in ancestry‐adjusted and ‐unadjusted models. We examine theoretical expectations under different scenarios for population substructure; applying different regression models, verifying and generalizing using simulations, and exploring the findings in real‐world admixed populations. We show that admixture does not lead to confounding when the trait locus is tested directly in a single admixed population. However, if there is more complex population structure or a marker locus in linkage disequilibrium (LD) with the trait locus is tested, both global and local ancestry can be confounders. Additionally, we show the genotype parameters of adjusted and unadjusted models all provide tests for LD between the marker and trait locus, but in different contexts. The local ancestry adjusted model tests for LD in the ancestral populations, while tests using the unadjusted and the global ancestry adjusted models depend on LD in the admixed population(s), which may be enriched due to different ancestral allele frequencies. Practically, this implies that global‐ancestry adjustment should be used for screening, but local‐ancestry adjustment may better inform fine mapping and provide better effect estimates at trait loci.