Strategies to design and analyze targeted sequencing data: cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study
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Strategies to design and analyze targeted sequencing data: cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study. / Lin, Honghuang; Wang, Min; Brody, Jennifer A; Bis, Joshua C; Dupuis, Josée; Lumley, Thomas; McKnight, Barbara; Rice, Kenneth M; Sitlani, Colleen M; Reid, Jeffrey G; Bressler, Jan; Liu, Xiaoming; Davis, Brian C; Johnson, Andrew D; O'Donnell, Christopher J; Kovar, Christie L; Dinh, Huyen; Wu, Yuanqing; Newsham, Irene; Chen, Han; Broka, Andi; DeStefano, Anita L; Gupta, Mayetri; Lunetta, Kathryn L; Liu, Ching-Ti; White, Charles C; Xing, Chuanhua; Zhou, Yanhua; Benjamin, Emelia J; Schnabel, Renate B; Heckbert, Susan R; Psaty, Bruce M; Muzny, Donna M; Cupples, L Adrienne; Morrison, Alanna C; Boerwinkle, Eric.
in: CIRC-CARDIOVASC GENE, Jahrgang 7, Nr. 3, 06.2014, S. 335-343.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Strategies to design and analyze targeted sequencing data: cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study
AU - Lin, Honghuang
AU - Wang, Min
AU - Brody, Jennifer A
AU - Bis, Joshua C
AU - Dupuis, Josée
AU - Lumley, Thomas
AU - McKnight, Barbara
AU - Rice, Kenneth M
AU - Sitlani, Colleen M
AU - Reid, Jeffrey G
AU - Bressler, Jan
AU - Liu, Xiaoming
AU - Davis, Brian C
AU - Johnson, Andrew D
AU - O'Donnell, Christopher J
AU - Kovar, Christie L
AU - Dinh, Huyen
AU - Wu, Yuanqing
AU - Newsham, Irene
AU - Chen, Han
AU - Broka, Andi
AU - DeStefano, Anita L
AU - Gupta, Mayetri
AU - Lunetta, Kathryn L
AU - Liu, Ching-Ti
AU - White, Charles C
AU - Xing, Chuanhua
AU - Zhou, Yanhua
AU - Benjamin, Emelia J
AU - Schnabel, Renate B
AU - Heckbert, Susan R
AU - Psaty, Bruce M
AU - Muzny, Donna M
AU - Cupples, L Adrienne
AU - Morrison, Alanna C
AU - Boerwinkle, Eric
N1 - © 2014 American Heart Association, Inc.
PY - 2014/6
Y1 - 2014/6
N2 - BACKGROUND: Genome-wide association studies have identified thousands of genetic variants that influence a variety of diseases and health-related quantitative traits. However, the causal variants underlying the majority of genetic associations remain unknown. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study aims to follow up genome-wide association study signals and identify novel associations of the allelic spectrum of identified variants with cardiovascular-related traits.METHODS AND RESULTS: The study included 4231 participants from 3 CHARGE cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, and the Framingham Heart Study. We used a case-cohort design in which we selected both a random sample of participants and participants with extreme phenotypes for each of 14 traits. We sequenced and analyzed 77 genomic loci, which had previously been associated with ≥1 of 14 phenotypes. A total of 52 736 variants were characterized by sequencing and passed our stringent quality control criteria. For common variants (minor allele frequency ≥1%), we performed unweighted regression analyses to obtain P values for associations and weighted regression analyses to obtain effect estimates that accounted for the sampling design. For rare variants, we applied 2 approaches: collapsed aggregate statistics and joint analysis of variants using the sequence kernel association test.CONCLUSIONS: We sequenced 77 genomic loci in participants from 3 cohorts. We established a set of filters to identify high-quality variants and implemented statistical and bioinformatics strategies to analyze the sequence data and identify potentially functional variants within genome-wide association study loci.
AB - BACKGROUND: Genome-wide association studies have identified thousands of genetic variants that influence a variety of diseases and health-related quantitative traits. However, the causal variants underlying the majority of genetic associations remain unknown. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study aims to follow up genome-wide association study signals and identify novel associations of the allelic spectrum of identified variants with cardiovascular-related traits.METHODS AND RESULTS: The study included 4231 participants from 3 CHARGE cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, and the Framingham Heart Study. We used a case-cohort design in which we selected both a random sample of participants and participants with extreme phenotypes for each of 14 traits. We sequenced and analyzed 77 genomic loci, which had previously been associated with ≥1 of 14 phenotypes. A total of 52 736 variants were characterized by sequencing and passed our stringent quality control criteria. For common variants (minor allele frequency ≥1%), we performed unweighted regression analyses to obtain P values for associations and weighted regression analyses to obtain effect estimates that accounted for the sampling design. For rare variants, we applied 2 approaches: collapsed aggregate statistics and joint analysis of variants using the sequence kernel association test.CONCLUSIONS: We sequenced 77 genomic loci in participants from 3 cohorts. We established a set of filters to identify high-quality variants and implemented statistical and bioinformatics strategies to analyze the sequence data and identify potentially functional variants within genome-wide association study loci.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Aging/genetics
KW - Cohort Studies
KW - Female
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Genomics
KW - Heart Diseases/epidemiology
KW - Humans
KW - Male
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Research Design
KW - Sequence Analysis, DNA
U2 - 10.1161/CIRCGENETICS.113.000350
DO - 10.1161/CIRCGENETICS.113.000350
M3 - SCORING: Journal article
C2 - 24951659
VL - 7
SP - 335
EP - 343
JO - CIRC-CARDIOVASC GENE
JF - CIRC-CARDIOVASC GENE
SN - 1942-325X
IS - 3
ER -