Dataset Information

NHLBI Atherosclerosis Risk in Communities (ARIC) Candidate Gene Association Resource (CARe)

ABSTRACT:

The Atherosclerosis Risk in Communities (ARIC) Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective epidemiologic study conducted in four U.S. communities. The four communities are Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date.

ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were reexamined every three years with the first screen (baseline) occurring in 1987-89, the second in 1990-92, the third in 1993-95, and the fourth and last exam was in 1996-98. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort.

In the Community Surveillance Component, currently ongoing, these four communities are investigated to determine the community-wide occurrence of hospitalized myocardial infarction and coronary heart disease deaths in men and women aged 35-84 years. Hospitalized stroke is investigated in cohort participants only. Starting in 2006, the study conducts community surveillance of inpatient (ages 55 years and older) and outpatient heart failure (ages 65 years and older) for heart failure events beginning in 2005.

NHLBI Candidate-gene Association Resource. The NHLBI initiated the Candidate gene Association Resource (CARe) to create a shared genotype/phenotype resource for analyses of the association of genotypes with phenotypes relevant to the mission of the NHLBI. The resource comprises nine cohort studies funded by the NHLBI including: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health Study (CHS), Cleveland Family Study (CFS), Coronary Artery Risk Development in Young Adults (CARDIA), Framingham Heart Study (FHS), Jackson Heart Study (JHS), Multi-Ethnic Study of Atherosclerosis (MESA), and the Sleep Heart Health Study (SHHS). A database of genotype and phenotype data was created that includes records for approximately 41,000 study participants with approximately 50,000 SNPs from more than 2,000 selected candidate genes. In addition, a genome wide association study using a 1,000K SNP Chip was conducted on approximately 8,900 African American participants drawn from five CARe cohorts: ARIC, CARDIA, CFS, JHS, and MESA. Data from individual cohorts is available to approved investigators through dbGaP.

Some relevant CARe publications
CARe Study: PMID 20400780
CVD Chip Design: PMID 18974833

OTHER RELATED OMICS DATASETS IN: MODEL1109130000MODEL1311110000MODEL1311110001MODEL1703310000

PROVIDER: phs000280.v1.p1 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Publications

Is early age-related maculopathy related to cognitive function? The Atherosclerosis Risk in Communities Study.

Wong Tien Yin TY Klein Ronald R Nieto F Javier FJ Moraes Suzana A D SA Mosley Thomas H TH Couper David J DJ Klein Barbara E K BE Boland Lori L LL Hubbard Larry D LD Sharrett A Richey AR

American journal of ophthalmology 20021201 6

<h4>Purpose</h4>Age-related maculopathy (ARM) and cognitive impairment are both neurodegenerative disorders associated with aging and have been hypothesized to share common pathogenic pathways. We describe the association between cognitive function and ARM in middle-aged persons.<h4>Design</h4>Population-based, cross-sectional study involving participants of the Atherosclerosis Risk in Communities Study, an ongoing cardiovascular investigation of persons 51 to 70 years of age, examined every 3 y ...[more]

PMID: 12470750

Publication: 1/558

Similar Datasets

Project description:The Atherosclerosis Risk in Communities (ARIC) Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective epidemiologic study conducted in four U.S. communities. The four communities are Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date. ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were examined with the baseline visit occurring in 1987-89, the second visit in 1990-92, the third visit in 1993-95, the fourth visit in 1996-98, and the fifth visit in 2011-13. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort. In the Community Surveillance Component, these four communities were investigated to determine the community-wide occurrence of hospitalized myocardial infarction and coronary heart disease deaths in men and women aged 35-84 years. Hospitalized stroke is investigated in cohort participants only. Starting in 2006, the study conducted community surveillance of inpatient (ages 55 years and older) and outpatient heart failure (ages 65 years and older) for heart failure events beginning in 2005. Community Surveillance for non-cohorts ended in event year 2014. ARIC is currently funded through October 31, 2021. The ARIC Cohort is utilized in the following dbGaP sub-studies. To view genotypes, other molecular data, and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" box located on the right hand side of this top-level study page <a href="study.cgi?study_id=phs000280">phs000280</a> ARIC Cohort. <ul> <li><a href="study.cgi?study_id=phs000557">phs000557</a> ARIC_CARe</li> <li><a href="study.cgi?study_id=phs000090">phs000090</a> GENEVA_ARIC</li> <li><a href="study.cgi?study_id=phs000223">phs000223</a> PAGE_CALiCo_ARIC</li> <li><a href="study.cgi?study_id=phs000398">phs000398</a> GO-ESP: HeartGo_ARIC</li> <li><a href="study.cgi?study_id=phs000668">phs000668</a> CHARGE_ARIC</li> <li><a href="study.cgi?study_id=phs000860">phs000860</a> MICORTEX</li> </ul>

Project description:The Atherosclerosis Risk in Communities (ARIC) Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective epidemiologic study conducted in four U.S. communities. The four communities are Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date. ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were reexamined every three years with the first screen (baseline) occurring in 1987-89, the second in 1990-92, the third in 1993-95, and the fourth and last exam was in 1996-98. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort. In the Community Surveillance Component, currently ongoing, these four communities are investigated to determine the community-wide occurrence of hospitalized myocardial infarction and coronary heart disease deaths in men and women aged 35-84 years. Hospitalized stroke is investigated in cohort participants only. Starting in 2006, the study conducts community surveillance of inpatient (ages 55 years and older) and outpatient heart failure (ages 65 years and older) for heart failure events beginning in 2005. ARIC is currently funded through January 31, 2012. This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to atherosclerosis and cardiovascular disease through large-scale genome-wide association studies of well-characterized cohorts of adults in four defined populations. Genotyping was performed at the Broad Institute of MIT and Harvard, a GENEVA genotyping center. Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

Project description:The Jackson Heart Study (JHS) is a large, community-based, observational study whose participants were recruited from urban and rural areas of the three counties (Hinds, Madison and Rankin) that make up the Jackson, Mississippi, metropolitan statistical area (MSA). Participants were enrolled from each of 4 recruitment pools: random, 17%; volunteer, 30%; currently enrolled in the Atherosclerosis Risk in Communities (ARIC) Study, 22% and secondary family members, 31%. Recruitment was limited to non-institutionalized adult African Americans 35-84 years old, except in the family cohort where those 21 to 34 years of age were eligible. The final cohort of 5,301 participants includes 6.59% of all African American Jackson MSA residents aged 35-84 (N-76,426, US Census 2000). Major components of each exam include medical history, physical examination, blood/urine analytes and interview questions on areas such as: physical activity; stress, coping and spirituality; racism and discrimination; socioeconomic position; and access to health care. At 12-month intervals after the baseline clinic visit (Exam 1), participants are contacted by telephone to: update information; confirm vital statistics; document interim medical events, hospitalizations, and functional status; and obtain additional sociocultural information. Questions about medical events, symptoms of cardiovascular disease and functional status are repeated annually. Ongoing cohort surveillance includes abstraction of medical records and death certificates for relevant International Classification of Diseases (ICD) codes and adjudication of nonfatal events and deaths. NHLBI Candidate-gene Association Resource. The NHLBI initiated the Candidate gene Association Resource (CARe) to create a shared genotype/phenotype resource for analyses of the association of genotypes with phenotypes relevant to the mission of the NHLBI. The resource comprises nine cohort studies funded by the NHLBI including: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health Study (CHS), Cleveland Family Study (CFS), Coronary Artery Risk Development in Young Adults (CARDIA), Framingham Heart Study (FHS), Jackson Heart Study (JHS), Multi-Ethnic Study of Atherosclerosis (MESA), and the Sleep Heart Health Study (SHHS). A database of genotype and phenotype data was created that includes records for approximately 41,000 study participants with approximately 50,000 SNPs from more than 2,000 selected candidate genes. In addition, a genome wide association study using a 1,000K SNP Chip was conducted on approximately 8,900 African American participants drawn from five CARe cohorts: ARIC, CARDIA, CFS, JHS, and MESA. Data from individual cohorts is available to approved investigators through dbGaP. Some relevant CARe publications CARe Study: PMID <a href="http://www.ncbi.nlm.nih.gov/pubmed/20400780" target="_blank">20400780</a> CVD Chip Design: PMID <a href="http://www.ncbi.nlm.nih.gov/pubmed/18974833" target="_blank">18974833</a>

Project description:HEK293 cells with CRISPR KO were analyzed using RNA-Seq. Abstract: Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is not currently understood. One such mechanism may be through regulation of nuclear gene expression via the modification of nuclear DNA (nDNA) methylation. To investigate this hypothesis, we assessed the relationship between mtDNA-CN and nDNA methylation in 2,507 African American (AA) and European Americans (EA) participants from the Atherosclerosis Risk in Communities (ARIC) study using the Infinium Human Methylation 450K Beadchip (485,764 CpGs). Thirty-four independent CpGs were associated with mtDNA-CN at genome-wide significance (P<5x10-8). To validate our findings we assayed an additional 2,528 participants from the Cardiovascular Health Study (CHS) (N=533) and Framingham Heart Study (FHS) (N=1995). Meta-analysis across all cohorts identified 6 mtDNA-CN associated CpGs to be validated across cohorts at genome-wide significance (P<5x10-8). Additionally, over half of these CpGs were associated with phenotypes known to be associated with mtDNA-CN, including CHD, CVD, and mortality. Experimental modification of mtDNA-CN through knockout via CRISPR-Cas9 of TFAM, a regulator of mtDNA replication, demonstrated that modulation of mtDNA-CN directly drives changes in nDNA methylation and gene expression of specific CpGs and nearby transcripts. Strikingly, the ‘neuroactive ligand receptor interaction’ KEGG pathway was found to be highly overrepresented in the ARIC cohort (P= 5.24x10-12), as well as the TFAM knockout methylation (P=4.41x10-4) and expression (P=4.30x10-4) studies. These results demonstrate that changes in mtDNA-CN influence nDNA methylation at specific loci and result in differential gene expression of specific genes, including those acting in the ‘neuroactive ligand receptor interaction’ pathway that may impact human health and disease via altered cell signaling.

Project description:Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is not currently understood. One such mechanism may be through regulation of nuclear gene expression via the modification of nuclear DNA (nDNA) methylation. To investigate this hypothesis, we assessed the relationship between mtDNA-CN and nDNA methylation in 2,507 African American (AA) and European Americans (EA) participants from the Atherosclerosis Risk in Communities (ARIC) study using the Infinium Human Methylation 450K Beadchip (485,764 CpGs). Thirty-four independent CpGs were associated with mtDNA-CN at genome-wide significance (P<5x10-8). To validate our findings we assayed an additional 2,528 participants from the Cardiovascular Health Study (CHS) (N=533) and Framingham Heart Study (FHS) (N=1995). Meta-analysis across all cohorts identified 6 mtDNA-CN associated CpGs to be validated ac ross cohorts at genome-wide significance (P<5x10-8). Additionally, over half of these CpGs were associated with phenotypes known to be associated with mtDNA-CN, including CHD, CVD, and mortality. Experimental modification of mtDNA-CN through knockout via CRISPR-Cas9 of TFAM, a regulator of mtDNA replication, demonstrated that modulation of mtDNA-CN directly drives changes in nDNA methylation and gene expression of specific CpGs and nearby transcripts. Strikingly, the ‘neuroactive ligand receptor interaction’ KEGG pathway was found to be highly overrepresented in the ARIC cohort (P= 5.24x10-12), as well as the TFAM knockout methylation (P=4.41x10-4) and expression (P=4.30x10-4) studies. These results demonstrate that changes in mtDNA-CN influence nDNA methylation at specific loci and result in differential gene expression of specific genes, including those acting in the ‘neuroactive ligand receptor interaction’ pathway that may impact human health and disease via altered cell signaling.

Dataset Information

NHLBI Atherosclerosis Risk in Communities (ARIC) Candidate Gene Association Resource (CARe)

Publications

Is early age-related maculopathy related to cognitive function? The Atherosclerosis Risk in Communities Study.

Similar Datasets

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