uu.seUppsala universitets publikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults
Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.
Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.
Lund Univ, Skåne Univ Hosp, Div Oncol & Pathol.
Lund Univ, Skåne Univ Hosp, Div Oncol & Pathol.
Vise andre og tillknytning
2017 (engelsk)Inngår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 46, nr 4, s. 1211-1222Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids.

Methods: Participants from the GLACIER Study (N-max = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms;replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (Delta TC) and triglycerides (Delta TG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; N-max = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N similar to 190 000) and functional annotation for the top ranking variants.

Results: In total, 956 variants were associated (P < 0.01) with either Delta TC or Delta TG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with Delta TG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 x 10(-8)), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 x 10(-6)). The rs7412 variant at APOE was associated with DTC in GLACIER (P < 1.7 x 10(-6)). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with Delta TC and for Delta TG, respectively (P < 10(-3)). Of these, a variant at CAPN3 (P = 1.2 x 10(-4)), multiple variants at HPR (P-min = 1.5 x 10(-6)) and a variant at SIX5 (P = 1.9 x 10(-4)) showed evidence for association with CAD.

Conclusions: We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk.

sted, utgiver, år, opplag, sider
2017. Vol. 46, nr 4, s. 1211-1222
Emneord [en]
Prospective cohort study, longitudinal analysis, total cholesterol, morbidity, triglycerides, single nucleotide polymorphism, genetic epidemiology
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-335751DOI: 10.1093/ije/dyw245ISI: 000411078800023PubMedID: 27864399OAI: oai:DiVA.org:uu-335751DiVA, id: diva2:1163898
Forskningsfinansiär
Swedish Research Council, 2012-1397Swedish Heart Lung Foundation, 20120197Novo NordiskSwedish Diabetes AssociationKnut and Alice Wallenberg FoundationRegion SkåneEU, European Research Council, 649021Tilgjengelig fra: 2017-12-08 Laget: 2017-12-08 Sist oppdatert: 2018-01-13bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekstPubMed

Personposter BETA

Gustafsson, StefanLind, LarsIngelsson, Erik

Søk i DiVA

Av forfatter/redaktør
Gustafsson, StefanLind, LarsIngelsson, Erik
Av organisasjonen
I samme tidsskrift
International Journal of Epidemiology

Søk utenfor DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 17 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf