Journal article
Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries
Nature communications, Vol.9(1), pp.2606-2606
07/04/2018
DOI: 10.1038/s41467-018-04668-w
PMCID: PMC6031652
PMID: 29973585
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.
Details
- Title: Subtitle
- Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries
- Creators
- Seyedeh M. Zekavat - Yale UniversitySanni Ruotsalainen - University of HelsinkiRobert E. Handsaker - Broad InstituteMaris Alver - University of TartuJonathan Bloom - Broad InstituteTimothy Poterba - Broad InstituteCotton Seed - Broad InstituteJason Ernst - University of California, Los AngelesMark Chaffin - Broad InstituteJesse Engreitz - Broad InstituteGina M. Peloso - Boston UniversityAni Manichaikul - University of VirginiaChaojie Yang - University of VirginiaKathleen A. Ryan - University of Maryland, BaltimoreMao Fu - University of Maryland, BaltimoreW. Craig Johnson - University of WashingtonMichael Tsai - University of MinnesotaMatthew Budoff - University of California, Los AngelesVasan S. Ramachandran - Boston UniversityJerome I. Rotter - University of California, Los AngelesStephen S. Rich - University of VirginiaWendy Post - Johns Hopkins UniversityBraxton D. Mitchell - University of Maryland, BaltimoreAdolfo Correa - University of MississippiAndres Metspalu - Estonian Genome Ctr, Tallinn, EstoniaJames G. Wilson - University of MississippiVeikko Salomaa - Finnish Institute for Health and WelfareManolis Kellis - Massachusetts Institute of TechnologyMark J. Daly - Broad InstituteBenjamin M. Neale - Broad InstituteSteven McCarroll - Broad InstituteIda Surakka - University of HelsinkiTonu Esko - Broad InstituteAndrea Ganna - Broad InstituteSamuli Ripatti - Broad InstituteSekar Kathiresan - Broad InstitutePradeep Natarajan - Broad InstituteNHLBI TOPMed Lipids Working GroupKarin F Hoth - Psychiatry
- Contributors
- Karin Hoth (Contributor) - University of Iowa, PsychiatryRobert Wallace (Contributor) - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.9(1), pp.2606-2606
- DOI
- 10.1038/s41467-018-04668-w
- PMID
- 29973585
- PMCID
- PMC6031652
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- R01 HG002898 / NHGRI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) R01HG002898 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) R01DK075787 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) K08 HL140203; R01 HL138737; R01 HL142711; R01 HL112064; K01 HL130609 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01 DK075787 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) T32 GM007205; U54 GM115428; P20 GM121334 / NIGMS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) P20GM121334 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) K01HL130609 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 07/04/2018
- Academic Unit
- Psychiatry; Epidemiology; Iowa Neuroscience Institute; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984293757502771
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