Global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk [S]

Abnormal plasma apolipoprotein levels are consistently implicated in CVD risk. Although 30% to 60% of their interindividual variability is genetic, common genetic variants explain only 10% to 20% of these differences. Rare genetic variants may be major sources of the missing heritability, yet quanti...
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Gespeichert in:

Autor*in:	Yitian Zhou [verfasserIn] Reedik Mägi [verfasserIn] Lili Milani [verfasserIn] Volker M. Lauschke [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	cholesterol lipid traits Alzheimer's disease population genetics

Übergeordnetes Werk:	In: Journal of Lipid Research - Elsevier, 2021, 59(2018), 10, Seite 1987-2000
Übergeordnetes Werk:	volume:59 ; year:2018 ; number:10 ; pages:1987-2000

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1194/jlr.P086710

Katalog-ID:	DOAJ050471341

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520			\|a Abnormal plasma apolipoprotein levels are consistently implicated in CVD risk. Although 30% to 60% of their interindividual variability is genetic, common genetic variants explain only 10% to 20% of these differences. Rare genetic variants may be major sources of the missing heritability, yet quantitative evaluations of their contribution to phenotypic variability are lacking. Here, we analyzed whole-genome and whole-exome sequencing data from 138,632 individuals across seven major human populations to present a systematic overview of genetic apolipoprotein variability. We provide population-specific frequencies of 38 clinically important apolipoprotein alleles and identify further 6,875 genetic variants, 33% of which are novel and 98.7% of which are rare with minor allele frequencies <1%. We predicted the functional impact of rare variants and found that their relative importance differed drastically between genes and among ethnicities. Importantly, we validated the clinical relevance of multiple variants with predicted effects by leveraging association data from the CARDIoGRAM (Coronary Artery Disease Genomewide Replication and Meta-analysis) and Global Lipids Genetics consortia. Overall, we provide a consolidated overview of population-specific apolipoprotein genetics as a valuable data resource for scientists and clinicians, estimate the importance of rare genetic variants for the missing heritability of apolipoprotein-associated disease traits, and pinpoint multiple novel apolipoprotein variants with putative population-specific impacts on serum lipid levels.
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language	English
source	In Journal of Lipid Research 59(2018), 10, Seite 1987-2000 volume:59 year:2018 number:10 pages:1987-2000
sourceStr	In Journal of Lipid Research 59(2018), 10, Seite 1987-2000 volume:59 year:2018 number:10 pages:1987-2000
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	cholesterol lipid traits Alzheimer's disease population genetics Biochemistry
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container_title	Journal of Lipid Research
authorswithroles_txt_mv	Yitian Zhou @@aut@@ Reedik Mägi @@aut@@ Lili Milani @@aut@@ Volker M. Lauschke @@aut@@
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callnumber-first	Q - Science
author	Yitian Zhou
spellingShingle	Yitian Zhou misc QD415-436 misc cholesterol misc lipid traits misc Alzheimer's disease misc population genetics misc Biochemistry Global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk [S]
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topic_title	QD415-436 Global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk [S] cholesterol lipid traits Alzheimer's disease population genetics
topic	misc QD415-436 misc cholesterol misc lipid traits misc Alzheimer's disease misc population genetics misc Biochemistry
topic_unstemmed	misc QD415-436 misc cholesterol misc lipid traits misc Alzheimer's disease misc population genetics misc Biochemistry
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title	Global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk [S]
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title_full	Global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk [S]
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title_sort	global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk [s]
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title_auth	Global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk [S]
abstract	Abnormal plasma apolipoprotein levels are consistently implicated in CVD risk. Although 30% to 60% of their interindividual variability is genetic, common genetic variants explain only 10% to 20% of these differences. Rare genetic variants may be major sources of the missing heritability, yet quantitative evaluations of their contribution to phenotypic variability are lacking. Here, we analyzed whole-genome and whole-exome sequencing data from 138,632 individuals across seven major human populations to present a systematic overview of genetic apolipoprotein variability. We provide population-specific frequencies of 38 clinically important apolipoprotein alleles and identify further 6,875 genetic variants, 33% of which are novel and 98.7% of which are rare with minor allele frequencies <1%. We predicted the functional impact of rare variants and found that their relative importance differed drastically between genes and among ethnicities. Importantly, we validated the clinical relevance of multiple variants with predicted effects by leveraging association data from the CARDIoGRAM (Coronary Artery Disease Genomewide Replication and Meta-analysis) and Global Lipids Genetics consortia. Overall, we provide a consolidated overview of population-specific apolipoprotein genetics as a valuable data resource for scientists and clinicians, estimate the importance of rare genetic variants for the missing heritability of apolipoprotein-associated disease traits, and pinpoint multiple novel apolipoprotein variants with putative population-specific impacts on serum lipid levels.
abstractGer	Abnormal plasma apolipoprotein levels are consistently implicated in CVD risk. Although 30% to 60% of their interindividual variability is genetic, common genetic variants explain only 10% to 20% of these differences. Rare genetic variants may be major sources of the missing heritability, yet quantitative evaluations of their contribution to phenotypic variability are lacking. Here, we analyzed whole-genome and whole-exome sequencing data from 138,632 individuals across seven major human populations to present a systematic overview of genetic apolipoprotein variability. We provide population-specific frequencies of 38 clinically important apolipoprotein alleles and identify further 6,875 genetic variants, 33% of which are novel and 98.7% of which are rare with minor allele frequencies <1%. We predicted the functional impact of rare variants and found that their relative importance differed drastically between genes and among ethnicities. Importantly, we validated the clinical relevance of multiple variants with predicted effects by leveraging association data from the CARDIoGRAM (Coronary Artery Disease Genomewide Replication and Meta-analysis) and Global Lipids Genetics consortia. Overall, we provide a consolidated overview of population-specific apolipoprotein genetics as a valuable data resource for scientists and clinicians, estimate the importance of rare genetic variants for the missing heritability of apolipoprotein-associated disease traits, and pinpoint multiple novel apolipoprotein variants with putative population-specific impacts on serum lipid levels.
abstract_unstemmed	Abnormal plasma apolipoprotein levels are consistently implicated in CVD risk. Although 30% to 60% of their interindividual variability is genetic, common genetic variants explain only 10% to 20% of these differences. Rare genetic variants may be major sources of the missing heritability, yet quantitative evaluations of their contribution to phenotypic variability are lacking. Here, we analyzed whole-genome and whole-exome sequencing data from 138,632 individuals across seven major human populations to present a systematic overview of genetic apolipoprotein variability. We provide population-specific frequencies of 38 clinically important apolipoprotein alleles and identify further 6,875 genetic variants, 33% of which are novel and 98.7% of which are rare with minor allele frequencies <1%. We predicted the functional impact of rare variants and found that their relative importance differed drastically between genes and among ethnicities. Importantly, we validated the clinical relevance of multiple variants with predicted effects by leveraging association data from the CARDIoGRAM (Coronary Artery Disease Genomewide Replication and Meta-analysis) and Global Lipids Genetics consortia. Overall, we provide a consolidated overview of population-specific apolipoprotein genetics as a valuable data resource for scientists and clinicians, estimate the importance of rare genetic variants for the missing heritability of apolipoprotein-associated disease traits, and pinpoint multiple novel apolipoprotein variants with putative population-specific impacts on serum lipid levels.
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title_short	Global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk [S]
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