Abstract P358: Discovery Loci and Generalization of Platelet Count Associations in the Hispanic Community Health Study: Study of Latinos (HCHS/SoL)

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Chani J Hodonsky ◽  
Ursula Schick ◽  
Jean Morrison ◽  
Cathy Laurie ◽  
John H Eckfeldt ◽  
...  
Keyword(s):  
Platelet Count ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Structural Integrity ◽  
Genome Wide Association Study ◽  
Genetic Model ◽  
The United States ◽  
Actin Binding ◽  
Health Study ◽  
A Genome

Background: The biology of platelets_anuclear megakaryocyte fragments required for clotting_is well defined, with abnormalities resulting in clotting disorders ranging from asymptomatic to severe. Although platelet count (PLT) is highly heritable (h 2 =0.57 in NHANES), genetic regulation of this trait remains incompletely characterized. In particular, Hispanic Latinos are a diverse population in which the genetic variability of PLT has not been analyzed. We aimed to 1) identify novel loci associated with PLT in participants of HCHS/SoL; and 2) determine if previously identified PLT loci generalize to the Hispanic Latino population. Methods: We performed a genome-wide association study of PLT in 12,491 participants of HCHS/SoL, which includes individuals with Dominican, Puerto Rican, Mexican, Cuban, South American, and Central American ancestral origins residing in the United States. Participants were genotyped on the Illumina SoL Omni2.5M array and imputed to the 1000 Genomes Phase I Reference panel. We implemented linear mixed-model regression assuming an additive genetic model, adjusting for sex, age, study center, ancestry and sample weights, and including random effects for individual relatedness, household, and block group. Results: Ten independent loci were significantly (α = 5x10 -8 ) associated with PLT in HCHS/SoL and 13 of 57 previously identified platelet-count GWAS loci generalized to HCHS/SoL (+/-500kb, α = 8.78x10 -4 ). Discovery loci included a significant association near GABBR1 (rs3131857, MAF = 40%, β = -0.16) and a suggestive association near ETV7 (rs9470264, MAF = 20%, β = -0.19). Furthermore, a noncoding variant in ACTN1 was associated with increased PLT (rs117672662, MAF = 6%, β = 0.61); ACTN1 codes for alpha-actinin, a multi-isoform actin-binding protein involved in cytoskeleton organization and platelet/megakaryocyte structural integrity. Missense mutations in ACTN1 were recently implicated in congenital thrombocytopenia; exome sequencing also associated this locus with PLT, which supports a potential functional role in PLT for this gene. Conditional regression analyses to assess secondary association signals are in progress. Conclusions: Genetic associations in two discovery loci ( ETV7 and GABBR1 ) underscore the benefit of using diverse populations in GWAS. Expanding the number of loci associated with platelet count will help elucidate disease mechanisms and develop approaches to treat platelet disorders in populations of all ancestries.

scholarly journals Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL Study

2021 ◽  
Author(s):  
Anne E. Justice ◽  
Kristin Young ◽  
Stephanie M. Gogarten ◽  
Tamar Sofer ◽  
Misa Graff ◽  
...  
Keyword(s):  
Central Obesity ◽  
Large Scale ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Genome Wide Association Study ◽  
Health Concern ◽  
Health Study ◽  
Central Adiposity ◽  
Combined Analysis ◽  
Genome Wide

AbstractCentral obesity is a leading health concern with a great burden carried by ethnic minority populations, and especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aim to: 1) identify novel loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC), and hip circumference (HIP), all adjusted for body mass index (adjBMI), using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); 2) determine if differences in genetic associations differ by background group within HCHS/SOL; 3) determine whether previously reported association regions generalize to HCHS/SOL. Our analyses included 7,472 women and 5,200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban, and Dominican) background residing in the US, with genome-wide array data imputed to the 1000 genomes Phase I multiethnic reference panel. We analyzed associations stratified by sex in addition to sexes combined using linear mixed-model regression. We identified 16 variants for WHRadjBMI, 22 for WCadjBMI, and 28 for HIPadjBMI that reached suggestive significance (P<1×10−6). Many of the loci exhibited differences in strength of associations by ethnic background and sex. We brought a total of 66 variants forward for validation in nine cohort studies (N=34,161) with participants of Hispanic/Latino, African and European descent. We confirmed four novel loci (ancestry-specific P<0.05 in replication, consistent direction of effect with HCHS/SOL, and P<5×10−8 after meta-analysis with HCHS/SOL), including rs13301996 in the sexes-combined analysis, and rs79478137 for women-only for WHRadjBMI; rs28692724 in women-only for HIPadjBMI; and rs3168072 in the sexes combined analysis for WCadjBMI. Also, a total of eight previously reported WHRadjBMI association regions, 12 for HIPadjBMI, and 10 for WCadjBMI generalized to HCHS/SOL. Our study findings highlight the importance of large-scale genomic studies in ancestrally diverse Hispanic/Latino populations for identifying and characterizing central obesity-susceptibility that may be ancestry-specific.

Hyperketonemia GWAS and parity-dependent SNP associations in Holstein dairy cows intensively sampled for blood β-hydroxybutyrate concentration

2020 ◽  
Vol 52 (8) ◽  
pp. 347-357
Author(s):  
Ryan S. Pralle ◽  
Nichol E. Schultz ◽  
Heather M. White ◽  
Kent A. Weigel
Keyword(s):  
Dairy Cows ◽  
Metabolic Pathways ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
A Genome ◽  
Screening Protocol ◽  
Control Procedures ◽  
Nuclear Polymorphism

Hyperketonemia (HYK) is a metabolic disorder that affects early postpartum dairy cows; however, there has been limited success in identifying genomic variants contributing to HYK susceptibility. We conducted a genome-wide association study (GWAS) using HYK phenotypes based on an intensive screening protocol, interrogated genotype interactions with parity group (GWIS), and evaluated the enrichment of annotated metabolic pathways. Holstein cows were enrolled into the experiment after parturition, and blood samples were collected at four timepoints between 5 and 18 days postpartum. Concentration of blood β-hydroxybutyrate (BHB) was quantified cow-side via a handheld BHB meter. Cows were labeled as a HYK case when at least one blood sample had BHB ≥ 1.2 mmol/L, and all other cows were considered non-HYK controls. After quality control procedures, 1,710 cows and 58,699 genotypes were available for further analysis. The GWAS and GWIS were performed using the forward feature select linear mixed model method. There was evidence for an association between ARS-BFGL-NGS-91238 and HYK susceptibility, as well as parity-dependent associations to HYK for BovineHD0600024247 and BovineHD1400023753. Candidate genes annotated to these single nuclear polymorphism associations have been previously associated with obesity, diabetes, insulin resistance, and fatty liver in humans and rodent models. Enrichment analysis revealed focal adhesion and axon guidance as metabolic pathways contributing to HYK etiology, while genetic variation in pathways related to insulin secretion and sensitivity may affect HYK susceptibility in a parity-dependent matter. In conclusion, the present work proposes several novel marker associations and metabolic pathways contributing to genetic risk for HYK susceptibility.

scholarly journals Genomic analysis of European bovine Staphylococcus aureus from clinical versus subclinical mastitis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jurriaan Hoekstra ◽  
Aldert L. Zomer ◽  
Victor P. M. G. Rutten ◽  
Lindert Benedictus ◽  
Arjan Stegeman ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Outcome ◽  
Virulence Genes ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Genome Wide Association Study ◽  
Bovine Mastitis ◽  
Subclinical Mastitis ◽  
Clinical Severity ◽  
A Genome

Abstract Intramammary infections (IMI) with Staphylococcus aureus are a common cause of bovine mastitis and can result in both clinical (CM) or subclinical mastitis (SCM). Although bacterial isolates of S. aureus differ in their virulence potential it is largely unclear which bacterial virulence factors are responsible for increased clinical severity. We performed a genome wide association study and used a generalized linear mixed model to investigate the correlation between gene carriage, lineage and clinical outcome of IMI in a collection of S. aureus isolates from cattle with CM (n = 125) and SCM (n = 151) from 11 European countries. An additional aim was to describe the genetic variation of bovine S. aureus in Europa. The dominant lineages in our collection were clonal complex (CC) 151 (81/276, 29.3%), CC97 (54/276, 19.6%), CC479 (32/276, 11.6%) and CC398 (19/276, 6.9%). Virulence and antimicrobial resistance (AMR) gene carriage was highly associated with CC. Among a selection of nine virulence and AMR genes, CC151, CC479 and CC133 carried more virulence genes than other CCs, and CC398 was associated with AMR gene carriage. Whereas CC151, CC97 were widespread in Europe, CC479, CC398 and CC8 were only found in specific countries. Compared to CC151, CC479 was associated with CM rather than SCM (OR 3.62; 95% CI 1.38–9.50) and the other CCs were not. Multiple genes were associated with CM, but due to the clustering within CC of carriage of these genes, it was not possible to differentiate between the effect of gene carriage and CC on clinical outcome of IMI. Nevertheless, this study demonstrates that characterization of S. aureus CC and virulence genes helps to predict the likelihood of the occurrence of CM following S. aureus IMI and highlights the potential benefit of diagnostics tools to identify S. aureus CC during bovine mastitis.

scholarly journals Influencing cardiovascular health habits in the rural, deep south: results of a cluster randomized trial

2019 ◽  
Vol 34 (2) ◽  
pp. 200-208
Author(s):  
Laurie S Abbott ◽  
Elizabeth H Slate ◽  
Jennifer L Lemacks
Keyword(s):  
Health Program ◽  
Mixed Model ◽  
Cardiovascular Health ◽  
Linear Mixed Model ◽  
Intervention Group ◽  
The United States ◽  
Control Group ◽  
Cvd Risk ◽  
Health Habits ◽  
Cluster Randomized

Abstract Cardiovascular disease (CVD) is a major cause of death among people living in the United States. Populations, especially minorities, living in the rural South are disproportionately affected by CVD and have greater CVD risk, morbidity and mortality. Culturally relevant cardiovascular health programs implemented in rural community settings can potentially reduce CVD risk and facilitate health behavior modification. The purpose of this study was to examine the effects of a cardiovascular health promotion intervention on the health habits of a group of rural African American adults. The study had a cluster randomized controlled trial design involving 12 rural churches that served as statistical clusters. From the churches (n = 6) randomized to the intervention group, 115 participants were enrolled, received the 6-week health program and completed pretest–posttest measures. The 114 participants from the control group churches (n = 6) did not receive the health program and completed the same pretest–posttest measures. The linear mixed model was used to compare group differences from pretest to posttest. The educational health intervention positively influenced select dietary and confidence factors that may contribute toward CVD risk reduction.

A Genetic Model To Predict Response to Glatiramer Acetate Developed from a Genome Wide Association Study (GWAS) (IN3-2.003)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. IN3-2.003-IN3-2.003
Author(s):  
F. Macciardi ◽  
J. Cohen ◽  
M. Comabella Lopez ◽  
G. Comi ◽  
G. Cutter ◽  
...  
Keyword(s):  
Association Study ◽  
Glatiramer Acetate ◽  
Genome Wide Association Study ◽  
Genetic Model ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-wide association study implicates CHRNA2 in cannabis use disorder

2017 ◽  
Author(s):  
Ditte Demontis ◽  
Veera Manikandan Rajagopal ◽  
Thomas D. Als ◽  
Jakob Grove ◽  
Jonatan Pallesen ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Significant Risk ◽  
The United States ◽  
Cannabis Use ◽  
Genome Wide Association ◽  
Cannabis Use Disorder ◽  
Genome Wide ◽  
Independent Population ◽  
A Genome

Introductory paragraphCannabis is the most frequently used illicit psychoactive substance worldwide1. Life time use has been reported among 35-40% of adults in Denmark2 and the United States3. Cannabis use is increasing in the population4–6 and among users around 9% become dependent7. The genetic risk component is high with heritability estimates of 518–70%9. Here we report the first genome-wide significant risk locus for cannabis use disorder (CUD, P=9.31×10−12) that replicates in an independent population (Preplication=3.27×10−3, Pmetaanalysis=9.09×10−12). The finding is based on a genome-wide association study (GWAS) of 2,387 cases and 48,985 controls followed by replication in 5,501 cases and 301,041 controls. The index SNP (rs56372821) is a strong eQTL for CHRNA2 and analyses of the genetic regulated gene expressions identified significant association of CHRNA2 expression in cerebellum with CUD. This indicates a potential therapeutic use in CUD of compounds with agonistic effect on the neuronal acetylcholine receptor alpha-2 subunit encoded by CHRNA2. At the polygenic level analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance.

scholarly journals Genome-wide association study reveals 14 new SNPs and confirms two structural variants highly associated with the horned/polled phenotype in goats

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiazhong Guo ◽  
Rui Jiang ◽  
Ayi Mao ◽  
George E. Liu ◽  
Siyuan Zhan ◽  
...  
Keyword(s):  
Association Study ◽  
Mixed Model ◽  
Genome Wide Association Study ◽  
Insertion Site ◽  
Genome Wide Association ◽  
Chromosome 1 ◽  
Structural Variants ◽  
Diagnostic Pcr ◽  
Genome Wide ◽  
A Genome

Abstract Background There is a long-term interest in investigating the genetic basis of the horned/polled phenotype in domestic goats. Here, we report a genome-wide association study (GWAS) to detect the genetic loci affecting the polled phenotype in goats. Results We obtained a total of 13,980,209 biallelic SNPs, using the genotyping-by-sequencing data from 45 Jintang Black (JT) goats, which included 32 female and nine male goats, and four individuals with the polled intersex syndrome (PIS). Using a mixed-model based GWAS, we identified two association signals, which were located at 150,334,857–150,817,260 bp (P = 5.15 × 10− 119) and 128,286,704–131,306,537 bp (P = 2.74 × 10− 15) on chromosome 1. The genotype distributions of the 14 most significantly associated SNPs were completely correlated with horn status in goats, based on the whole-genome sequencing (WGS) data from JT and two other Chinese horned breeds. However, variant annotation suggested that none of the detected SNPs within the associated regions were plausible causal mutations. Via additional read-depth analyses and visual inspections of WGS data, we found a 10.1-kb deletion (CHI1:g. 129424781_129434939del) and a 480-kb duplication (CHI1:150,334,286–150,818,098 bp) encompassing two genes KCNJ15 and ERG in the associated regions of polled and PIS-affected goats. Notably, the 10.1-kb deletion also served as the insertion site for the 480-kb duplication, as validated by PCR and Sanger sequencing. Our WGS genotyping showed that all horned goats were homozygous for the reference alleles without either the structural variants (SVs), whereas the PIS-affected goats were homozygous for both the SVs. We also demonstrated that horned, polled, and PIS-affected individuals among 333 goats from JT and three other Chinese horned breeds can be accurately classified via PCR amplification and agarose gel electrophoresis of two fragments in both SVs. Conclusion Our results revealed that two genomic regions on chromosome 1 are major loci affecting the polled phenotypes in goats. We provided a diagnostic PCR to accurately classify horned, polled, and PIS-affected goats, which will enable a reliable genetic test for the early-in-life prediction of horn status in goats.

scholarly journals Robots Versus Humans: Automated Annotation Accurately Quantifies Essential Ocean Variables of Rocky Intertidal Functional Groups and Habitat State

2021 ◽  
Vol 8 ◽  
Author(s):  
Gonzalo Bravo ◽  
Nicolas Moity ◽  
Edgardo Londoño-Cruz ◽  
Frank Muller-Karger ◽  
Gregorio Bigatti ◽  
...  
Keyword(s):  
Machine Learning ◽  
Functional Groups ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Visual Analysis ◽  
Gulf Of Maine ◽  
The United States ◽  
Marine Biodiversity ◽  
Percent Cover ◽  
Automated Annotation

Standardized methods for effectively and rapidly monitoring changes in the biodiversity of marine ecosystems are critical to assess status and trends in ways that are comparable between locations and over time. In intertidal and subtidal habitats, estimates of fractional cover and abundance of organisms are typically obtained with traditional quadrat-based methods, and collection of photoquadrat imagery is a standard practice. However, visual analysis of quadrats, either in the field or from photographs, can be very time-consuming. Cutting-edge machine learning tools are now being used to annotate species records from photoquadrat imagery automatically, significantly reducing processing time of image collections. However, it is not always clear whether information is lost, and if so to what degree, using automated approaches. In this study, we compared results from visual quadrats versus automated photoquadrat assessments of macroalgae and sessile organisms on rocky shores across the American continent, from Patagonia (Argentina), Galapagos Islands (Ecuador), Gorgona Island (Colombian Pacific), and the northeast coast of the United States (Gulf of Maine) using the automated software CoralNet. Photoquadrat imagery was collected at the same time as visual surveys following a protocol implemented across the Americas by the Marine Biodiversity Observation Network (MBON) Pole to Pole of the Americas program. Our results show that photoquadrat machine learning annotations can estimate percent cover levels of intertidal benthic cover categories and functional groups (algae, bare substrate, and invertebrate cover) nearly identical to those from visual quadrat analysis. We found no statistical differences of cover estimations of dominant groups in photoquadrat images annotated by humans and those processed in CoralNet (binomial generalized linear mixed model or GLMM). Differences between these analyses were not significant, resulting in a Bray-Curtis average distance of 0.13 (sd 0.11) for the full label set, and 0.12 (sd 0.14) for functional groups. This is the first time that CoralNet automated annotation software has been used to monitor “Invertebrate Abundance and Distribution” and “Macroalgal Canopy Cover and Composition” Essential Ocean Variables (EOVs) in intertidal habitats. We recommend its use for rapid, continuous surveys over expanded geographical scales and monitoring of intertidal areas globally.

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