title: Genetic analysis of 16 NMR-lipoprotein fractions in humans, the GOLDN study.
abstract: Sixteen nuclear magnetic resonance (NMR) spectroscopy lipoprotein measurements of more than 1,000 subjects of GOLDN study, at fasting and at 3.5 and 6 h after a postprandial fat (PPL) challenge at visits 2 and 4, before and after a 3 weeks Fenofibrate (FF) treatment, were included in 6 time-independent multivariate factor analyses. Their top 1,541 unique SNPs were assessed for association with GOLDN NMR-particles and classical lipids. Several SNPs with -log₁₀ p > 7.3 and MAF ≥ 0.10, mostly intergenic associated with NMR-single traits near genes FAM84B (8q24.21), CRIPT (2p21), ACOXL (2q13), BCL2L11 (2q13), PCDH10 (4q28.3), NXPH1 (7p22), and SLC24A4 (14q32.12) in association with NMR-LDLs; HOMER1 (5q14.2), KIT (4q11-q12), VSNL1 (2p24.3), QPRT (16p11.2), SYNPR (3p14.2), NXPH1 (7p22), NELL1 (11p15.1), and RUNX3 (1p36) with NMR-HDLs; and DOK5-CBLN4-MC3R (20q13), NELL1 (11p15.1), STXBP6 (14q12), APOB (2p24-p23), GPR133 (12q24.33), FAM84B (8q24.21) and NR5A2 (1q32.1) in association with NMR-VLDLs particles. NMR single traits associations produced 75 % of 114 significant candidates, 7 % belonged to classical lipids and 18 % overlapped, and 16 % matched for time of discovery between NMR- and classical traits. Five proxy genes, (ACOXL, FAM84B, NXPH1, STK40 and VAPA) showed pleiotropic effects. While tagged for significant associations in our study and with some extra evidence from the literature, candidates as CBNL4, FAM84B, NXPH1, SLC24A4 remain unclear for their functional relation to lipid metabolism. Although GOLDN study is one of the largest in studying PPL and FF treatment effects, the relatively small samples (over 700-1,000 subjects) in association tests appeals for a replication of such a study. Thus, further investigation is needed.
authors.affiliation: Division of Statistical Genomics, Washington University School of Medicine, 4444 Forest Park Ave, Campus Box 8506, St. Louis, MO 63108, USA. aldi@wustl.edu
authors.forename: Aldi T
authors.initials: AT
authors.lastname: Kraja
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Frazier-Wood
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Straka
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Province
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
mesh_terms: D000328:Adult; D005215:Fasting; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period / Q000187:drug effects*
chemical_list: D000960:Hypolipidemic Agents; D008074:Lipoproteins; D011345:Fenofibrate