Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Replicative and non-replicative mechanisms in the formation of clustered CNVs are indicated by whole genome characterization

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Human genetic variation in GLS2 is associated with development of complicated Staphylococcus aureus bacteremia

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Genetic anticipation in Swedish Lynch syndrome families

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Low prevalence of retinopathy among Greenland Inuit

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. A large remaining potential in lipid-lowering drug treatment in the type 2 diabetes population: A Danish nationwide cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Fatty acids (FAs) are involved in cellular processes important for normal body function, and perturbation of FA balance has been linked to metabolic disturbances, including type 2 diabetes. An individual's level of FAs is affected by diet, lifestyle, and genetic variation. We aimed to improve the understanding of the mechanisms and pathways involved in regulation of FA tissue levels, by identifying genetic loci associated with inter-individual differences in erythrocyte membrane FA levels. We assessed the levels of 22 FAs in the phospholipid fraction of erythrocyte membranes from 2,626 Greenlanders in relation to single nucleotide polymorphisms genotyped on the MetaboChip or imputed. We identified six independent association signals. Novel loci were identified on chromosomes 5 and 11 showing strongest association with oleic acid (rs76430747 in ACSL6, beta (SE): -0.386% (0.034), p = 1.8x10-28) and docosahexaenoic acid (rs6035106 in DTD1, 0.137% (0.025), p = 6.4x10-8), respectively. For a missense variant (rs80356779) in CPT1A, we identified a number of novel FA associations, the strongest with 11-eicosenoic acid (0.473% (0.035), p = 2.6x10-38), and for variants in FADS2 (rs174570), LPCAT3 (rs2110073), and CERS4 (rs11881630) we replicated known FA associations. Moreover, we observed metabolic implications of the ACSL6 (rs76430747) and CPT1A (rs80356779) variants, which both were associated with altered HbA1c (0.051% (0.013), p = 5.6x10-6 and -0.034% (0.016), p = 3.1x10-4, respectively). The latter variant was also associated with reduced insulin resistance (HOMA-IR, -0.193 (0.050), p = 3.8x10-6), as well as measures of smaller body size, including weight (-2.676 kg (0.523), p = 2.4x10-7), lean mass (-1.200 kg (0.271), p = 1.7x10-6), height (-0.966 cm (0.230), p = 2.0x10-5), and BMI (-0.638 kg/m2 (0.181), p = 2.8x10-4). In conclusion, we have identified novel genetic determinants of FA composition in phospholipids in erythrocyte membranes, and have shown examples of links between genetic variants associated with altered FA membrane levels and changes in metabolic traits.

Original languageEnglish
JournalP L o S Genetics
Volume12
Issue number6
Pages (from-to)e1006119
ISSN1553-7390
DOIs
Publication statusPublished - 24 Jun 2016
Externally publishedYes

    Research areas

  • Body Size, Carnitine O-Palmitoyltransferase, Coenzyme A Ligases, Diabetes Mellitus, Type 2, Docosahexaenoic Acids, Erythrocyte Membrane, Fatty Acids, Fatty Acids, Monounsaturated, Female, Genetic Loci, Genotype, Greenland, Hemoglobin A, Glycosylated, Humans, Insulin, Insulin Resistance, Male, Oleic Acid, Phospholipids, Polymorphism, Single Nucleotide, Journal Article, Research Support, Non-U.S. Gov't

ID: 51445501