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Joint effect of genetic and lifestyle risk factors on type 2 diabetes risk among Chinese men and women.

Abstract More than 40 genetic susceptibility loci have been reported for type 2 diabetes (T2D). Recently, the combined effect of genetic variants has been investigated by calculating a genetic risk score. We evaluated 36 genome-wide association study (GWAS) identified SNPs in 2,679 T2D cases and 3322 controls in middle-age Han Chinese. Fourteen SNPs were significantly associated with T2D in analysis adjusted for age, sex and BMI. We calculated two genetic risk scores (GRS) (GRS1 with all the 36 SNPs and GRS2 with the 14 SNPs significantly associated with T2D). The odds ratio for T2D with each GRS point (per risk allele) was 1.08 (95% CI: 1.06-1.09) for GRS1 and 1.15 (95% CI: 1.13-1.18) for GRS2. The OR for quintiles were 1.00, 1.26, 1.69, 1.95 and 2.18 (P<0.0001) for GRS1 and 1.00, 1.33, 1.60, 2.03 and 2.80 (P<0.001) for GRS2. Participants in the higher tertile of GRS1 and the higher BMI category had a higher risk of T2D compared to those on the lower tertiles of the GRS1 and of BMI (OR = 11.08; 95% CI: 7.39-16.62). We found similar results when we investigated joint effects between GRS1 and WHR terciles and exercise participation. We finally investigated the joint effect between tertiles of GRSs and a composite high risk score (no exercise participation and high BMI and WHR) on T2D risk. We found that compared to participants with low GRS1 and no high risk factors for T2D, those with high GRS1 and three high risk factors had a higher risk of T2D (OR = 13.06; 95% CI: 8.65-19.72) but the interaction factor was of marginal significance. The association was accentuated when we repeated analysis with the GRS2. In conclusion we found an association between GRS and lifestyle factors, alone and in combination, contributed to the risk of and T2D among middle age Chinese.
PMID
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Authors

Mayor MeshTerms

Genetic Predisposition to Disease

Life Style

Keywords
Journal Title plos one
Publication Year Start




PMID- 23185337
OWN - NLM
STAT- MEDLINE
DCOM- 20130522
LR  - 20161019
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 11
DP  - 2012
TI  - Joint effect of genetic and lifestyle risk factors on type 2 diabetes risk among 
      Chinese men and women.
PG  - e49464
LID - 10.1371/journal.pone.0049464 [doi]
AB  - More than 40 genetic susceptibility loci have been reported for type 2 diabetes
      (T2D). Recently, the combined effect of genetic variants has been investigated by
      calculating a genetic risk score. We evaluated 36 genome-wide association study
      (GWAS) identified SNPs in 2,679 T2D cases and 3322 controls in middle-age Han
      Chinese. Fourteen SNPs were significantly associated with T2D in analysis
      adjusted for age, sex and BMI. We calculated two genetic risk scores (GRS) (GRS1 
      with all the 36 SNPs and GRS2 with the 14 SNPs significantly associated with
      T2D). The odds ratio for T2D with each GRS point (per risk allele) was 1.08 (95% 
      CI: 1.06-1.09) for GRS1 and 1.15 (95% CI: 1.13-1.18) for GRS2. The OR for
      quintiles were 1.00, 1.26, 1.69, 1.95 and 2.18 (P&lt;0.0001) for GRS1 and 1.00,
      1.33, 1.60, 2.03 and 2.80 (P&lt;0.001) for GRS2. Participants in the higher tertile 
      of GRS1 and the higher BMI category had a higher risk of T2D compared to those on
      the lower tertiles of the GRS1 and of BMI (OR = 11.08; 95% CI: 7.39-16.62). We
      found similar results when we investigated joint effects between GRS1 and WHR
      terciles and exercise participation. We finally investigated the joint effect
      between tertiles of GRSs and a composite high risk score (no exercise
      participation and high BMI and WHR) on T2D risk. We found that compared to
      participants with low GRS1 and no high risk factors for T2D, those with high GRS1
      and three high risk factors had a higher risk of T2D (OR = 13.06; 95% CI:
      8.65-19.72) but the interaction factor was of marginal significance. The
      association was accentuated when we repeated analysis with the GRS2. In
      conclusion we found an association between GRS and lifestyle factors, alone and
      in combination, contributed to the risk of and T2D among middle age Chinese.
FAU - Villegas, Raquel
AU  - Villegas R
AD  - Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University
      Medical Center, Nashville, Tennessee, United States of America.
      [email protected]
FAU - Delahanty, Ryan
AU  - Delahanty R
FAU - Gao, Yu-Tang
AU  - Gao YT
FAU - Long, Jirong
AU  - Long J
FAU - Williams, Scott M
AU  - Williams SM
FAU - Xiang, Yong-Bing
AU  - Xiang YB
FAU - Cai, Hui
AU  - Cai H
FAU - Li, Hong-Lan
AU  - Li HL
FAU - Hu, Frank
AU  - Hu F
FAU - Cai, Qiuyin
AU  - Cai Q
FAU - Zheng, Wei
AU  - Zheng W
FAU - Shu, Xiao-Ou
AU  - Shu XO
LA  - eng
GR  - 1 UL1 RR024975/RR/NCRR NIH HHS/United States
GR  - R01 DK058845/DK/NIDDK NIH HHS/United States
GR  - R01 CA122756/CA/NCI NIH HHS/United States
GR  - R01CA64277/CA/NCI NIH HHS/United States
GR  - BC050791/BC/NCI NIH HHS/United States
GR  - R01CA122756/CA/NCI NIH HHS/United States
GR  - R01CA92585/CA/NCI NIH HHS/United States
GR  - P30 CA68485/CA/NCI NIH HHS/United States
GR  - R37 CA070867/CA/NCI NIH HHS/United States
GR  - DK58845/DK/NIDDK NIH HHS/United States
GR  - HG004399/HG/NHGRI NIH HHS/United States
GR  - R01 CA092585/CA/NCI NIH HHS/United States
GR  - R01 CA070867/CA/NCI NIH HHS/United States
GR  - R01 CA090899/CA/NCI NIH HHS/United States
GR  - R01CA100374/CA/NCI NIH HHS/United States
GR  - R01 CA064277/CA/NCI NIH HHS/United States
GR  - K01 DK082639/DK/NIDDK NIH HHS/United States
GR  - R37CA70867/CA/NCI NIH HHS/United States
GR  - R01 CA118229/CA/NCI NIH HHS/United States
GR  - R01 CA124558/CA/NCI NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
GR  - R01CA90899/CA/NCI NIH HHS/United States
GR  - R01CA124558/CA/NCI NIH HHS/United States
GR  - U01 HG004399/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20121121
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anthropometry
MH  - Body Height
MH  - Body Weight
MH  - China
MH  - Diabetes Mellitus, Type 2/*diagnosis/*genetics
MH  - Exercise
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Humans
MH  - *Life Style
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Reproducibility of Results
MH  - Risk
MH  - Risk Factors
PMC - PMC3504028
EDAT- 2012/11/28 06:00
MHDA- 2013/05/23 06:00
CRDT- 2012/11/28 06:00
PHST- 2012/07/17 00:00 [received]
PHST- 2012/10/09 00:00 [accepted]
PHST- 2012/11/28 06:00 [entrez]
PHST- 2012/11/28 06:00 [pubmed]
PHST- 2013/05/23 06:00 [medline]
AID - 10.1371/journal.pone.0049464 [doi]
AID - PONE-D-12-21614 [pii]
PST - ppublish
SO  - PLoS One. 2012;7(11):e49464. doi: 10.1371/journal.pone.0049464. Epub 2012 Nov 21.