Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction
Ron Do,Ron Do,Nathan O. Stitziel,Hong-Hee Won,Hong-Hee Won,Anders Berg Jørgensen,Stefano Duga,Pier Angelica Merlini,Adam Kiezun,Martin Farrall,Anuj Goel,Or Zuk,Illaria Guella,Rosanna Asselta,Leslie A. Lange,Gina M. Peloso,Gina M. Peloso,Paul L. Auer,Domenico Girelli,Nicola Martinelli,Deborah N. Farlow,Mark A. DePristo,Robert Roberts,Alex Stewart,Danish Saleheen,John Danesh,Stephen E. Epstein,Suthesh Sivapalaratnam,G. Kees Hovingh,John J.P. Kastelein,Nilesh J. Samani,Heribert Schunkert,Jeanette Erdmann,Svati H. Shah,William E. Kraus,Robert W. Davies,Majid Nikpay,Christopher T. Johansen,Jian Wang,Robert A. Hegele,Eliana Hechter,Winfried März,Winfried März,Winfried März,Marcus E. Kleber,Jie Huang,Andrew D. Johnson,Mingyao Li,Greg L. Burke,Myron D. Gross,Yongmei Liu,Themistocles L. Assimes,Gerardo Heiss,Ethan M. Lange,Aaron R. Folsom,Herman A. Taylor,Oliviero Olivieri,Anders Hamsten,Robert Clarke,Dermot F. Reilly,Wu Yin,Manuel A. Rivas,Peter Donnelly,Jacques E. Rossouw,Bruce M. Psaty,Bruce M. Psaty,David M. Herrington,James G. Wilson,Stephen S. Rich,Michael J. Bamshad,Russell P. Tracy,L. Adrienne Cupples,Daniel J. Rader,Muredach P. Reilly,John A. Spertus,Sharon Cresci,Jaana Hartiala,W.H. Wilson Tang,Stanley L. Hazen,Hooman Allayee,Alexander P. Reiner,Alexander P. Reiner,Christopher S. Carlson,Charles Kooperberg,Rebecca D. Jackson,Eric Boerwinkle,Eric S. Lander,Stephen M. Schwartz,Stephen M. Schwartz,David S. Siscovick,Ruth McPherson,Anne Tybjærg-Hansen,Gonçalo R. Abecasis,Hugh Watkins,Deborah A. Nickerson,Diego Ardissino,Shamil R. Sunyaev,Shamil R. Sunyaev,Christopher J. O'Donnell,David Altshuler,David Altshuler,Stacey Gabriel,Sekar Kathiresan,Sekar Kathiresan +103 more
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Kathiresan et al. as mentioned in this paper used exome sequencing of nearly 10,000 people to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk.Abstract:
Exome sequence analysis of nearly 10,000 people was carried out to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk, identifying the key roles of low-density lipoprotein cholesterol and metabolism of triglyceride-rich lipoproteins. Sekar Kathiresan and colleagues use exome sequencing of nearly 10,000 people to probe the contribution of multiple rare mutations within a gene to risk for myocardial infarction at a population level. They find that mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) are associated with disease risk. When compared with non-carriers, LDLR mutation carriers had higher plasma levels of LDL cholesterol, whereas APOA5 mutation carriers had higher plasma levels of triglycerides. As well as confirming that APOA5 is a myocardial infarction gene, this work informs the design and conduct of rare-variant association studies for complex diseases. Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance1,2. When MI occurs early in life, genetic inheritance is a major component to risk1. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families3,4,5,6,7,8, whereas common variants at more than 45 loci have been associated with MI risk in the population9,10,11,12,13,14,15. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol16. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl−1. At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase15,17 and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.read more
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A comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease
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References
More filters
Journal ArticleDOI
The Sequence Alignment/Map format and SAMtools
Heng Li,Bob Handsaker,Alec Wysoker,T. J. Fennell,Jue Ruan,Nils Homer,Gabor T. Marth,Gonçalo R. Abecasis,Richard Durbin +8 more
TL;DR: SAMtools as discussed by the authors implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments.
Journal ArticleDOI
Fast and accurate short read alignment with Burrows–Wheeler transform
Heng Li,Richard Durbin +1 more
TL;DR: Burrows-Wheeler Alignment tool (BWA) is implemented, a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps.
Journal ArticleDOI
PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Shaun Purcell,Shaun Purcell,Benjamin M. Neale,Benjamin M. Neale,Kathe Todd-Brown,Lori Thomas,Manuel A. R. Ferreira,David Bender,David Bender,Julian Maller,Julian Maller,Pamela Sklar,Pamela Sklar,Paul I.W. de Bakker,Paul I.W. de Bakker,Mark J. Daly,Mark J. Daly,Pak C. Sham +17 more
TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
Journal ArticleDOI
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
TL;DR: The ANNOVAR tool to annotate single nucleotide variants and insertions/deletions, such as examining their functional consequence on genes, inferring cytogenetic bands, reporting functional importance scores, finding variants in conserved regions, or identifying variants reported in the 1000 Genomes Project and dbSNP is developed.
Journal ArticleDOI
A framework for variation discovery and genotyping using next-generation DNA sequencing data
Mark A. DePristo,Eric Banks,Ryan Poplin,Kiran V. Garimella,Jared Maguire,Christopher Hartl,Anthony A. Philippakis,Anthony A. Philippakis,Anthony A. Philippakis,Guillermo del Angel,Manuel A. Rivas,Manuel A. Rivas,Matt Hanna,Aaron McKenna,Timothy Fennell,Andrew Kernytsky,Andrey Sivachenko,Kristian Cibulskis,Stacey Gabriel,David Altshuler,David Altshuler,Mark J. Daly,Mark J. Daly +22 more
TL;DR: A unified analytic framework to discover and genotype variation among multiple samples simultaneously that achieves sensitive and specific results across five sequencing technologies and three distinct, canonical experimental designs is presented.
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Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.
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