8 results on '"NHLBI TOPMed Lipids Working Group"'
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2. Publisher Correction: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.
- Author
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Zekavat, Seyedeh M, Ruotsalainen, Sanni, Handsaker, Robert E, Alver, Maris, Bloom, Jonathan, Poterba, Timothy, Seed, Cotton, Ernst, Jason, Chaffin, Mark, Engreitz, Jesse, Peloso, Gina M, Manichaikul, Ani, Yang, Chaojie, Ryan, Kathleen A, Fu, Mao, Johnson, W Craig, Tsai, Michael, Budoff, Matthew, Vasan, Ramachandran S, Cupples, L Adrienne, Rotter, Jerome I, Rich, Stephen S, Post, Wendy, Mitchell, Braxton D, Correa, Adolfo, Metspalu, Andres, Wilson, James G, Salomaa, Veikko, Kellis, Manolis, Daly, Mark J, Neale, Benjamin M, McCarroll, Steven, Surakka, Ida, Esko, Tonu, Ganna, Andrea, Ripatti, Samuli, Kathiresan, Sekar, Natarajan, Pradeep, and NHLBI TOPMed Lipids Working Group
- Subjects
NHLBI TOPMed Lipids Working Group - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2020
3. Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.
- Author
-
Natarajan, Pradeep, Peloso, Gina M, Zekavat, Seyedeh Maryam, Montasser, May, Ganna, Andrea, Chaffin, Mark, Khera, Amit V, Zhou, Wei, Bloom, Jonathan M, Engreitz, Jesse M, Ernst, Jason, O'Connell, Jeffrey R, Ruotsalainen, Sanni E, Alver, Maris, Manichaikul, Ani, Johnson, W Craig, Perry, James A, Poterba, Timothy, Seed, Cotton, Surakka, Ida L, Esko, Tonu, Ripatti, Samuli, Salomaa, Veikko, Correa, Adolfo, Vasan, Ramachandran S, Kellis, Manolis, Neale, Benjamin M, Lander, Eric S, Abecasis, Goncalo, Mitchell, Braxton, Rich, Stephen S, Wilson, James G, Cupples, L Adrienne, Rotter, Jerome I, Willer, Cristen J, Kathiresan, Sekar, and NHLBI TOPMed Lipids Working Group
- Subjects
NHLBI TOPMed Lipids Working Group ,Humans ,Lipids ,Base Sequence ,Gene Frequency ,Mutation ,Genome ,Human ,Models ,Genetic ,Cholesterol ,LDL ,Genome-Wide Association Study ,High-Throughput Nucleotide Sequencing ,Human Genome ,Genetics ,Digestive Diseases ,Cardiovascular ,Atherosclerosis ,Biotechnology ,2.1 Biological and endogenous factors - Abstract
Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia.
- Published
- 2018
4. Publisher Correction: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.
- Author
-
Zekavat, Seyedeh M, Ruotsalainen, Sanni, Handsaker, Robert E, Alver, Maris, Bloom, Jonathan, Poterba, Timothy, Seed, Cotton, Ernst, Jason, Chaffin, Mark, Engreitz, Jesse, Peloso, Gina M, Manichaikul, Ani, Yang, Chaojie, Ryan, Kathleen A, Fu, Mao, Johnson, W Craig, Tsai, Michael, Budoff, Matthew, Vasan, Ramachandran S, Cupples, L Adrienne, Rotter, Jerome I, Rich, Stephen S, Post, Wendy, Mitchell, Braxton D, Correa, Adolfo, Metspalu, Andres, Wilson, James G, Salomaa, Veikko, Kellis, Manolis, Daly, Mark J, Neale, Benjamin M, McCarroll, Steven, Surakka, Ida, Esko, Tonu, Ganna, Andrea, Ripatti, Samuli, Kathiresan, Sekar, Natarajan, Pradeep, and NHLBI TOPMed Lipids Working Group
- Subjects
NHLBI TOPMed Lipids Working Group - Abstract
The original version of this article contained an error in the name of the author Ramachandran S. Vasan, which was incorrectly given as Vasan S. Ramachandran. This has now been corrected in both the PDF and HTML versions of the article.
- Published
- 2018
5. Publisher Correction: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.
- Author
-
Zekavat, Seyedeh M, Ruotsalainen, Sanni, Handsaker, Robert E, Alver, Maris, Bloom, Jonathan, Poterba, Timothy, Seed, Cotton, Ernst, Jason, Chaffin, Mark, Engreitz, Jesse, Peloso, Gina M, Manichaikul, Ani, Yang, Chaojie, Ryan, Kathleen A, Fu, Mao, Johnson, W Craig, Tsai, Michael, Budoff, Matthew, Vasan, Ramachandran S, Cupples, L Adrienne, Rotter, Jerome I, Rich, Stephen S, Post, Wendy, Mitchell, Braxton D, Correa, Adolfo, Metspalu, Andres, Wilson, James G, Salomaa, Veikko, Kellis, Manolis, Daly, Mark J, Neale, Benjamin M, McCarroll, Steven, Surakka, Ida, Esko, Tonu, Ganna, Andrea, Ripatti, Samuli, Kathiresan, Sekar, Natarajan, Pradeep, and NHLBI TOPMed Lipids Working Group
- Subjects
NHLBI TOPMed Lipids Working Group - Abstract
The original version of this article contained an error in the name of the author Ramachandran S. Vasan, which was incorrectly given as Vasan S. Ramachandran. This has now been corrected in both the PDF and HTML versions of the article.
- Published
- 2018
6. Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.
- Author
-
Natarajan, Pradeep, Peloso, Gina M, Zekavat, Seyedeh Maryam, Montasser, May, Ganna, Andrea, Chaffin, Mark, Khera, Amit V, Zhou, Wei, Bloom, Jonathan M, Engreitz, Jesse M, Ernst, Jason, O'Connell, Jeffrey R, Ruotsalainen, Sanni E, Alver, Maris, Manichaikul, Ani, Johnson, W Craig, Perry, James A, Poterba, Timothy, Seed, Cotton, Surakka, Ida L, Esko, Tonu, Ripatti, Samuli, Salomaa, Veikko, Correa, Adolfo, Vasan, Ramachandran S, Kellis, Manolis, Neale, Benjamin M, Lander, Eric S, Abecasis, Goncalo, Mitchell, Braxton, Rich, Stephen S, Wilson, James G, Cupples, L Adrienne, Rotter, Jerome I, Willer, Cristen J, Kathiresan, Sekar, and NHLBI TOPMed Lipids Working Group
- Subjects
NHLBI TOPMed Lipids Working Group ,Humans ,Lipids ,Base Sequence ,Gene Frequency ,Mutation ,Genome ,Human ,Models ,Genetic ,Cholesterol ,LDL ,Genome-Wide Association Study ,High-Throughput Nucleotide Sequencing ,Human Genome ,Digestive Diseases ,Cardiovascular ,Biotechnology ,Genetics ,Atherosclerosis ,2.1 Biological and endogenous factors ,Aetiology - Abstract
Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia.
- Published
- 2018
7. Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.
- Author
-
Zekavat, Seyedeh M, Ruotsalainen, Sanni, Handsaker, Robert E, Alver, Maris, Bloom, Jonathan, Poterba, Timothy, Seed, Cotton, Ernst, Jason, Chaffin, Mark, Engreitz, Jesse, Peloso, Gina M, Manichaikul, Ani, Yang, Chaojie, Ryan, Kathleen A, Fu, Mao, Johnson, W Craig, Tsai, Michael, Budoff, Matthew, Vasan, Ramachandran S, Cupples, L Adrienne, Rotter, Jerome I, Rich, Stephen S, Post, Wendy, Mitchell, Braxton D, Correa, Adolfo, Metspalu, Andres, Wilson, James G, Salomaa, Veikko, Kellis, Manolis, Daly, Mark J, Neale, Benjamin M, McCarroll, Steven, Surakka, Ida, Esko, Tonu, Ganna, Andrea, Ripatti, Samuli, Kathiresan, Sekar, Natarajan, Pradeep, and NHLBI TOPMed Lipids Working Group
- Subjects
NHLBI TOPMed Lipids Working Group ,Humans ,Cardiovascular Diseases ,Lipoprotein(a) ,Adaptor Proteins ,Vesicular Transport ,Risk Factors ,Gene Expression ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Genome ,Human ,African Continental Ancestry Group ,European Continental Ancestry Group ,Cholesterol ,LDL ,Genome-Wide Association Study ,DNA Copy Number Variations ,Whole Genome Sequencing ,Atherosclerosis ,Genetics ,Cardiovascular ,Prevention ,Human Genome ,Heart Disease ,2.1 Biological and endogenous factors - Abstract
Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.
- Published
- 2018
8. Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.
- Author
-
Zekavat, Seyedeh M, Ruotsalainen, Sanni, Handsaker, Robert E, Alver, Maris, Bloom, Jonathan, Poterba, Timothy, Seed, Cotton, Ernst, Jason, Chaffin, Mark, Engreitz, Jesse, Peloso, Gina M, Manichaikul, Ani, Yang, Chaojie, Ryan, Kathleen A, Fu, Mao, Johnson, W Craig, Tsai, Michael, Budoff, Matthew, Vasan, Ramachandran S, Cupples, L Adrienne, Rotter, Jerome I, Rich, Stephen S, Post, Wendy, Mitchell, Braxton D, Correa, Adolfo, Metspalu, Andres, Wilson, James G, Salomaa, Veikko, Kellis, Manolis, Daly, Mark J, Neale, Benjamin M, McCarroll, Steven, Surakka, Ida, Esko, Tonu, Ganna, Andrea, Ripatti, Samuli, Kathiresan, Sekar, Natarajan, Pradeep, and NHLBI TOPMed Lipids Working Group
- Subjects
NHLBI TOPMed Lipids Working Group ,Humans ,Cardiovascular Diseases ,Lipoprotein(a) ,Adaptor Proteins ,Vesicular Transport ,Risk Factors ,Gene Expression ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Genome ,Human ,Cholesterol ,LDL ,Genome-Wide Association Study ,DNA Copy Number Variations ,Whole Genome Sequencing ,White People ,Black People ,Genetics ,Prevention ,Heart Disease ,Human Genome ,Atherosclerosis ,Cardiovascular ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being - Abstract
Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.
- Published
- 2018
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