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Genetic Analysis of 16 NMR‐Lipoprotein Fractions in Humans, the GOLDN Study
Author(s) -
Kraja Aldi T.,
Borecki Ingrid B.,
Tsai Michael Y.,
Ordovas Jose M.,
Hopkins Paul N.,
Lai ChaoQiang,
FrazierWood Alexis C.,
Straka Robert J.,
Hixson James E.,
Province Michael A.,
Arnett Donna K.
Publication year - 2013
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-012-3740-8
Subject(s) - single nucleotide polymorphism , nuclear magnetic resonance spectroscopy , lipoprotein , genome wide association study , metabolomics , biology , chemistry , genetics , gene , biochemistry , cholesterol , bioinformatics , genotype , stereochemistry
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 −log 10 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 C BNL4, 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.