title: A genome-wide association study of saturated, mono- and polyunsaturated red blood cell fatty acids in the Framingham Heart Offspring Study.
abstract: Most genome-wide association studies have explored relationships between genetic variants and plasma phospholipid fatty acid proportions, but few have examined apparent genetic influences on the membrane fatty acid profile of red blood cells (RBC). Using RBC fatty acid data from the Framingham Offspring Study, we analyzed over 2.5 million single nucleotide polymorphisms (SNPs) for association with 14 RBC fatty acids identifying 191 different SNPs associated with at least 1 fatty acid. Significant associations (p<1×10(-8)) were located within five distinct 1MB regions. Of particular interest were novel associations between (1) arachidonic acid and PCOLCE2 (regulates apoA-I maturation and modulates apoA-I levels), and (2) oleic and linoleic acid and LPCAT3 (mediates the transfer of fatty acids between glycerolipids). We also replicated previously identified strong associations between SNPs in the FADS (chromosome 11) and ELOVL (chromosome 6) regions. Multiple SNPs explained 8-14% of the variation in 3 high abundance (>11%) fatty acids, but only 1-3% in 4 low abundance (<3%) fatty acids, with the notable exception of dihomo-gamma linolenic acid with 53% of variance explained by SNPs. Further studies are needed to determine the extent to which variations in these genes influence tissue fatty acid content and pathways modulated by fatty acids.
authors.affiliation: Department of Mathematics, Statistics and Computer Science, Dordt College, Sioux Center, IA 51250, USA. Electronic address: nathan.tintle@dordt.edu.
authors.forename: N L
authors.initials: NL
authors.lastname: Tintle
authors.affiliation: Health Diagnostic Laboratory, Richmond, VA, USA; Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: Pottala
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Ave., Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lacey
authors.affiliation: Framingham Heart Study, 73 Mt. Wayte Ave., Framingham, MA 01702, USA; Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA.
authors.forename: V
authors.initials: V
authors.lastname: Ramachandran
authors.affiliation: Department of Mathematics, Statistics and Computer Science, Dordt College, Sioux Center, IA 51250, USA.
authors.forename: J
authors.initials: J
authors.lastname: Westra
authors.affiliation: Department of Mathematics, Statistics and Computer Science, Dordt College, Sioux Center, IA 51250, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rogers
authors.affiliation: Department of Mathematics, Statistics and Computer Science, Dordt College, Sioux Center, IA 51250, USA.
authors.forename: J
authors.initials: J
authors.lastname: Clark
authors.affiliation: Department of Mathematics, Statistics and Computer Science, Dordt College, Sioux Center, IA 51250, USA.
authors.forename: B
authors.initials: B
authors.lastname: Olthoff
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Ave., Boston, MA, USA; Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Mathematics and Statistics, Boston University, 111 Cummington St., Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Larson
authors.affiliation: Health Diagnostic Laboratory, Richmond, VA, USA; Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA; OmegaQuant, Sioux Falls, SD, USA.
authors.forename: W
authors.initials: W
authors.lastname: Harris
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA, USA.
authors.forename: G C
authors.initials: GC
authors.lastname: Shearer
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000235:genetics; D000123:Acetyltransferases / Q000235:genetics; D000368:Aged; D002877:Chromosomes, Human / Q000235:genetics*; D004912:Erythrocytes / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000097:blood*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D016326:Extracellular Matrix Proteins; D005227:Fatty Acids; D006023:Glycoproteins; C491553:PCOLCE2 protein, human; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C543069:LPCAT3 protein, human
keywords: Arachidonic acid; Glycerol‐lipids; Linoleic acid; Oleic acid; PUFA; apoA-I maturation