25 research outputs found

    Genome-Wide Association Study of White Blood Cell Count in 16,388 African Americans: the Continental Origins and Genetic Epidemiology Network (COGENT)

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    Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived “null” variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5×10−8). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large inter-chromosomal duplications can result in false positive associations in GWAS

    52 Genetic Loci Influencing Myocardial Mass.

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    BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets

    Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

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    The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexit

    Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

    Get PDF
    The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity

    Feedback from the Field: Feasibility of the Perinatal Food Group Recall Form

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    Background: Maintaining a healthy weight can reduce risks of excessive weight gain during pregnancy and help prevent maternal and child obesity. Low-income women are high-risk for excessive weight gain during pregnancy. Nutrition counseling can help improve dietary habits, however, it is often provided by paraprofessionals who lack formal training in dietetics. There is a need for a brief dietary assessment form for paraprofessionals serving low-income perinatal women. Purpose: The purpose of this study was to provide feedback on the feasibility of the Perinatal Food Group Recall (PFGR) form among Comprehensive Perinatal Health Workers (CPHWs) serving low-income pregnant and post-partum mothers. Methods: Nine CPHWs at four clinics were asked to complete their regular dietary assessment form and then administer the PFGR. Key informant interviews with the nine paraprofessionals were conducted to obtain their feedback on the form. Results: The findings suggest that the form provides a feasible and easyto-administer dietary assessment tool for use by practitioners without formal dietetics training who serve clinics in low-income communities with heavy client flow. Conclusion: The form can facilitate the provision of nutrition counseling among low-income mothers and build capacity among community health workers

    Implementation of an Individual + Policy, System, and Environmental (I + PSE) Technical Assistance Initiative to Increase Capacity of MCH Nutrition Strategic Planning

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    IntroductionChildhood obesity disproportionately affects low-income women, children, racial/ethnic minorities, and rural populations. To effectively promote sustainable change, healthy eating and active living initiatives should apply individual plus policy, systems, and environmental (I + PSE) approaches.MethodsFour public health maternal and child nutrition teams selected through an application process participated in 12 months of technical assistance (TA) to develop action plans incorporating I + PSE in nutrition programming. TA included: (1) online modules; (2) community of practice (CoP) meetings; and (3) individual coaching sessions. Teams completed midpoint and endpoint surveys to assess TA knowledge and process outcomes. Semi-structured, in-depth interviews conducted post TA were transcribed and content analysis used to characterize themes and sub-themes.ResultsFacilitators to implementing I + PSE approaches included TA delivery through online modules, participation in the CoP, and individual coaching to address barriers to implementation and leadership support. Barriers were time and funding limitations, working in isolation, and lack of infrastructure and self-efficacy. Co-learning helped TA teams overcome stagnancy and promote development of creative solutions. Teams recognized relationship-building as integral to systems development.DiscussionLessons learned occurred across three main areas: relationships, capacity-building, and barriers encountered. Relationship formation takes time and is often not recognized as an asset impacting public health programing. Relationship direction - upstream, downstream, and lateral - affects ability to build organizational and systems capacity. While this study includes a small number of public health nutrition teams, this practice-based research highlights the value of I + PSE TA to tackle complex problems, with reciprocal, multisectoral support to enhance public health nutrition program impact

    Effect of a Targeted Subsidy on Intake of Fruits and Vegetables Among Low-Income Women in the Special Supplemental Nutrition Program for Women, Infants, and Children

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    Objectives. Intake of fruits and vegetables protects against several common chronic diseases, and low income is associated with lower intake. We tested the effectiveness of a subsidy for fruits and vegetables to the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
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