uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • 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.
Show others and affiliations
2017 (English)In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 46, no 4, p. 1211-1222Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
2017. Vol. 46, no 4, p. 1211-1222
Keyword [en]
Prospective cohort study, longitudinal analysis, total cholesterol, morbidity, triglycerides, single nucleotide polymorphism, genetic epidemiology
National Category
Occupational Health and Environmental Health Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:uu:diva-335751DOI: 10.1093/ije/dyw245ISI: 000411078800023PubMedID: 27864399OAI: oai:DiVA.org:uu-335751DiVA: diva2:1163898
Funder
Swedish Research Council, 2012-1397Swedish Heart Lung Foundation, 20120197Novo NordiskSwedish Diabetes AssociationKnut and Alice Wallenberg FoundationRegion SkåneEU, European Research Council, 649021
Available from: 2017-12-08 Created: 2017-12-08 Last updated: 2018-01-13Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Gustafsson, StefanLind, LarsIngelsson, Erik

Search in DiVA

By author/editor
Gustafsson, StefanLind, LarsIngelsson, Erik
By organisation
Science for Life Laboratory, SciLifeLabMolecular epidemiologyCardiovascular epidemiology
In the same journal
International Journal of Epidemiology
Occupational Health and Environmental HealthPublic Health, Global Health, Social Medicine and Epidemiology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 13 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf