PMID- 24725463
OWN - NLM
STAT- MEDLINE
DCOM- 20140826
LR  - 20221207
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 13
DP  - 2014 Apr 12
TI  - Analysis of common and coding variants with cardiovascular disease in the 
      Diabetes Heart Study.
PG  - 77
LID - 10.1186/1475-2840-13-77 [doi]
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major cardiovascular disease 
      (CVD) risk factor. Identification of genetic risk factors for CVD is important to 
      understand disease risk. Two recent genome-wide association study (GWAS) 
      meta-analyses in the Cohorts for Heart and Aging Research in Genomic Epidemiology 
      (CHARGE) consortium detected CVD-associated loci. METHODS: Variants identified in 
      CHARGE were tested for association with CVD phenotypes, including vascular 
      calcification, and conventional CVD risk factors, in the Diabetes Heart Study 
      (DHS) (n = 1208; >80% T2DM affected). This included 36 genotyped or imputed 
      single nucleotide polymorphisms (SNPs) from DHS GWAS data. 28 coding SNPs from 14 
      top CHARGE genes were also identified from exome sequencing resources and 
      genotyped, along with 209 coding variants from the Illumina HumanExome BeadChip 
      genotype data in the DHS were also tested. Genetic risk scores (GRS) were 
      calculated to evaluate the association of combinations of variants with CVD 
      measures. RESULTS: After correction for multiple comparisons, none of the CHARGE 
      SNPs were associated with vascular calcification (p < 0.0014). Multiple SNPs 
      showed nominal significance with calcification, including rs599839 (PSRC1, 
      p = 0.008), rs646776 (CELSR2, p = 0.01), and rs17398575 (PIK3CG, p = 0.009). 
      Additional COL4A2 and CXCL12 SNPs were nominally associated with all-cause or 
      CVD-cause mortality. Three SNPs were significantly or nominally associated with 
      serum lipids: rs3135506 (Ser19Trp, APOA5) with triglycerides (TG) (p = 5x10(-5)), 
      LDL (p = 0.00070), and nominally with high density lipoprotein (HDL) 
      (p = 0.0054); rs651821 (5'UTR, APOA5) with increased TGs (p = 0.0008); rs13832449 
      (splice donor, APOC3) associated with decreased TGs (p = 0.0015). Rs45456595 
      (CDKN2A, Gly63Arg), rs5128 (APOC3, 3'UTR), and rs72650673 (SH2B3, Glu400Lys) were 
      nominally associated with history of CVD, subclinical CVD, or CVD risk factors 
      (p < 0.010). From the exome chip, rs3750103 (CHN2, His204Arg/His68Arg) with 
      carotid intima-medial thickness (IMT) (p = 3.9x10(-5)), and rs61937878 (HAL, 
      Val549Met) with infra-renal abdominal aorta CP (AACP) (p = 7.1x10(-5)). The 
      unweighted GRS containing coronary artery calcified plaque (CAC) SNPs was 
      nominally associated with history of prior CVD (p = 0.033; OR = 1.09). The 
      weighted GRS containing SNPs was associated with CAC and myocardial infarction 
      (MI) was associated with history of MI (p = 0.026; OR = 1.15). CONCLUSIONS: 
      Genetic risk factors for subclinical CVD in the general population (CHARGE) were 
      modestly associated with T2DM-related risk factors and CVD outcomes in the DHS.
FAU - Adams, Jeremy N
AU  - Adams JN
FAU - Raffield, Laura M
AU  - Raffield LM
FAU - Freedman, Barry I
AU  - Freedman BI
FAU - Langefeld, Carl D
AU  - Langefeld CD
FAU - Ng, Maggie C Y
AU  - Ng MC
FAU - Carr, J Jeffrey
AU  - Carr JJ
FAU - Cox, Amanda J
AU  - Cox AJ
FAU - Bowden, Donald W
AU  - Bowden DW
AD  - Center for Genomics and Personalized Medicine Research, Wake Forest School of 
      Medicine, Winston-Salem, NC 27157, USA. dbowden@wakehealth.edu.
LA  - eng
GR  - R01 HL092301/HL/NHLBI NIH HHS/United States
GR  - R01 NS058700/NS/NINDS NIH HHS/United States
GR  - R01 HL67348/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140412
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
SB  - IM
MH  - Aged
MH  - Cardiovascular Diseases/diagnosis/epidemiology/*genetics
MH  - Diabetes Mellitus, Type 2/diagnosis/epidemiology/*genetics
MH  - Female
MH  - Follow-Up Studies
MH  - Genetic Variation/*genetics
MH  - Genome-Wide Association Study/*methods
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - White People/*genetics
PMC - PMC4021556
EDAT- 2014/04/15 06:00
MHDA- 2014/08/27 06:00
PMCR- 2014/04/12
CRDT- 2014/04/15 06:00
PHST- 2014/01/14 00:00 [received]
PHST- 2014/03/26 00:00 [accepted]
PHST- 2014/04/15 06:00 [entrez]
PHST- 2014/04/15 06:00 [pubmed]
PHST- 2014/08/27 06:00 [medline]
PHST- 2014/04/12 00:00 [pmc-release]
AID - 1475-2840-13-77 [pii]
AID - 10.1186/1475-2840-13-77 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2014 Apr 12;13:77. doi: 10.1186/1475-2840-13-77.