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Family-specific agg...
Family-specific aggregation of lipid GWAS variants confers the susceptibility to familial hypercholesterolemia in a large Austrian family
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Nikkola, E. (author)
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Ko, A. (author)
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Alvarez, M. (author)
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Cantor, R. M. (author)
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Garske, K. (author)
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Kim, E. (author)
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Gee, S. (author)
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Rodriguez, A. (author)
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Muxel, R. (author)
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Matikainen, N. (author)
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Soderlund, S. (author)
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Motazacker, M. M. (author)
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- Borén, Jan, 1963 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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Lamina, C. (author)
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Kronenberg, F. (author)
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Schneider, W. J. (author)
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Palotie, A. (author)
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Laakso, M. (author)
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Taskinen, M. R. (author)
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Pajukanta, P. (author)
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(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English.
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 264, s. 58-66
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Abstract
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- Background and aims: Hypercholesterolemia confers susceptibility to cardiovascular disease (CVD). Both serum total cholesterol (TC) and LDL-cholesterol (LDL-C) exhibit a strong genetic component (heritability estimates 0.41-0.50). However, a large part of this heritability cannot be explained by the variants identified in recent extensive genome-wide association studies (GWAS) on lipids. Our aim was to find genetic causes leading to high LDL-C levels and ultimately CVD in a large Austrian family presenting with what appears to be autosomal dominant inheritance for familial hypercholesterolemia (FH). Methods: We utilized linkage analysis followed by whole-exome sequencing and genetic risk score analysis using an Austrian multi-generational family with various dyslipidemias, including elevated TC and LDL-C, and one family branch with elevated lipoprotein (a) (Lp(a)). Results: We did not find evidence for genome-wide significant linkage for LDL-C or apparent causative variants in the known FH genes rather, we discovered a particular family-specific combination of nine GWAS LDL-C SNPs (p = 0.02 by permutation), and putative less severe familial hypercholesterolemia mutations in the LDLR and APOB genes in a subset of the affected family members. Separately, high Lp(a) levels observed in one branch of the family were explained primarily by the LPA locus, including short (< 23) Kringle IV repeats and rs3798220. Conclusions: Taken together, some forms of FH may be explained by family-specific combinations of LDL-C GWAS SNPs. (c) 2017 Elsevier B.V. All rights reserved.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Familial hypercholesterolemia (FH)
- LDL cholesterol
- Genetic risk score (GRS)
- Lipoprotein (a)
- atherosclerosis society
- lipoprotein(a)
- population
- phenotypes
- mutations
- disease
- management
- diagnosis
- genetics
- moderate
- Cardiovascular System & Cardiology
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Nikkola, E.
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Ko, A.
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Alvarez, M.
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Cantor, R. M.
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Garske, K.
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Kim, E.
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show more...
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Gee, S.
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Rodriguez, A.
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Muxel, R.
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Matikainen, N.
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Soderlund, S.
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Motazacker, M. M ...
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Borén, Jan, 1963
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Lamina, C.
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Kronenberg, F.
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Schneider, W. J.
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Palotie, A.
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Laakso, M.
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Taskinen, M. R.
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Pajukanta, P.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Atherosclerosis
- By the university
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University of Gothenburg