Circulation. Cardiovascular genetics
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Circ Cardiovasc Genet · Jun 2014
Meta AnalysisGenome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium.
Omega6 (n6) polyunsaturated fatty acids (PUFAs) and their metabolites are involved in cell signaling, inflammation, clot formation, and other crucial biological processes. Genetic components, such as variants of fatty acid desaturase (FADS) genes, determine the composition of n6 PUFAs. ⋯ Our findings suggest that along with the FADS gene cluster, additional genes may influence n6 PUFA composition.
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Circ Cardiovasc Genet · Jun 2014
ADAM19 and HTR4 variants and pulmonary function: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.
The pulmonary function measures of forced expiratory volume in 1 second (FEV1) and its ratio to forced vital capacity (FVC) are used in the diagnosis and monitoring of lung diseases and predict cardiovascular mortality in the general population. Genome-wide association studies (GWASs) have identified numerous loci associated with FEV1 and FEV1/FVC, but the causal variants remain uncertain. We hypothesized that novel or rare variants poorly tagged by GWASs may explain the significant associations between FEV1/FVC and 2 genes: ADAM19 and HTR4. ⋯ Sequencing identified 1 common variant associated with FEV1/FVC independent of the sentinel ADAM19 GWAS hit and supports the original HTR4 GWAS findings. Rare variants do not seem to underlie GWAS associations with pulmonary function for common variants in ADAM19 and HTR4.
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Circ Cardiovasc Genet · Jun 2014
Sequence variation in TMEM18 in association with body mass index: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.
Genome-wide association studies for body mass index (BMI) previously identified a locus near TMEM18. We conducted targeted sequencing of this region to investigate the role of common, low-frequency, and rare variants influencing BMI. ⋯ Targeted sequencing around TMEM18 identified 2 novel BMI variants with possible regulatory function.
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Circ Cardiovasc Genet · Jun 2014
Sequencing of 2 subclinical atherosclerosis candidate regions in 3669 individuals: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.
Atherosclerosis, the precursor to coronary heart disease and stroke, is characterized by an accumulation of fatty cells in the arterial intimal-medial layers. Common carotid intima media thickness (cIMT) and plaque are subclinical atherosclerosis measures that predict cardiovascular disease events. Previously, genome-wide association studies demonstrated evidence for association with cIMT (SLC17A4) and plaque (PIK3CG). ⋯ Common and rare variants in PIK3CG and SLC17A4 regions demonstrated modest association with subclinical atherosclerosis traits. Although not conclusive, these findings may help to understand the genetic architecture of regions previously implicated by genome-wide association studies and identify variants within these regions for further investigation in larger samples.
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Circ Cardiovasc Genet · Jun 2014
Association of levels of fasting glucose and insulin with rare variants at the chromosome 11p11.2-MADD locus: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.
Common variation at the 11p11.2 locus, encompassing MADD, ACP2, NR1H3, MYBPC3, and SPI1, has been associated in genome-wide association studies with fasting glucose and insulin (FI). In the Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted Sequencing Study, we sequenced 5 gene regions at 11p11.2 to identify rare, potentially functional variants influencing fasting glucose or FI levels. ⋯ Sequencing at 11p11.2-NR1H3 identified rare variation associated with FI. One variant, chr11:47227430, seems to be functional, with the rare A allele reducing transcription factor FOXA1 binding and FOXA1-dependent transcriptional activity.