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Genetic and Environmental Factors in Cardiometabolic Risk

Chen, Yan LU (2018) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2018(155).
Abstract
Abstract:
Cardiovascular diseases and diabetes mellitus are closely linked by sharing common risk factors, such as obesity, insulin resistance, hypertension and dyslipidaemia. These intermediate risk factors are affected by the joint effects of environment and genetics. Although a multitude of studies aimed to disentangle the effects of gene-environment interactions, many of the published gene-environment interaction analyses are inadequately powered and lack replication due to the small magnitude of interaction effect sizes. Meanwhile, many more potential gene-environment interactions affecting cardiometabolic risk are yet to be discovered. This thesis investigated the role of genetic and environmental factors in a range of... (More)
Abstract:
Cardiovascular diseases and diabetes mellitus are closely linked by sharing common risk factors, such as obesity, insulin resistance, hypertension and dyslipidaemia. These intermediate risk factors are affected by the joint effects of environment and genetics. Although a multitude of studies aimed to disentangle the effects of gene-environment interactions, many of the published gene-environment interaction analyses are inadequately powered and lack replication due to the small magnitude of interaction effect sizes. Meanwhile, many more potential gene-environment interactions affecting cardiometabolic risk are yet to be discovered. This thesis investigated the role of genetic and environmental factors in a range of cardiometabolic traits (e.g. body mass index (BMI), blood lipids, and blood pressure), using three complementary study designs.
In Paper I, two Swedish cohorts, the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk Study (GLACIER, N=4902) and the Malmö Diet and Cancer Study (MDCS, N=21,824) were analyzed. In the meta-analysis, a nominally significant interaction (Pint=0.03) was observed between sugar sweetened beverage (SSB) intake and a genetic risk score based on BMI related single nucleotide polymorphisms (SNPs). With SSB consumption defined as four categories, one SSB intake category increase was associated with 0.18 kg/m2 mean change of BMI (P= 1.7×10-20; n = 26,726).
In Paper II, interactions between dietary polyunsaturated fatty acid (PUFA) intake and variation at the fatty acid desaturase (FADS) gene cluster were investigated in the GLACIER cohort (N=5,160). In summary, SNP-, haplotype-, and gene-level interaction signals were observed in relation to serum triglyceride concentrations. Through functional annotation, the FADS2 rs5792235 SNP was identified as the probable causal variant in the region (owing to its high functionality score).
In Paper III, using repeated-measures data from >18,000 adults in a subcohort of the Västerbotten Health Survey, an environment-wide association study (EWAS) was performed employing linear mixed-models, assuming different intercepts for each individual. A varying number (12-75) of exposure variables showed environmental-wide-significant associations with nine cardiometabolic traits. For the first time, we showed that heptadecanoic acid (C17:0) is strongly associated with a range of cardiometabolic traits.
In conclusion, in this thesis I report novel and confirmatory evidence of environmental risk factors, as well as gene-environment interactions for major intermediate cardiometabolic risk factors. (Less)
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author
supervisor
opponent
  • professor Ma, Roland CW, The Chinese University of Hong Kong
organization
publishing date
type
Thesis
publication status
published
subject
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2018
issue
155
pages
76 pages
publisher
Lund University: Faculty of Medicine
defense location
Aulan, CRC, Jan Waldenströms gata 35, Skånes Universitetssjukhus i Malmö
defense date
2018-12-17 09:00:00
ISSN
1652-8220
ISBN
978-91-7619-724-0
language
English
LU publication?
yes
id
6a60b1b2-59c1-4e00-9430-51600a4101f2
date added to LUP
2019-01-14 04:08:38
date last changed
2019-11-19 13:49:46
@phdthesis{6a60b1b2-59c1-4e00-9430-51600a4101f2,
  abstract     = {Abstract: <br>
Cardiovascular diseases and diabetes mellitus are closely linked by sharing common risk factors, such as obesity, insulin resistance, hypertension and dyslipidaemia. These intermediate risk factors are affected by the joint effects of environment and genetics. Although a multitude of studies aimed to disentangle the effects of gene-environment interactions, many of the published gene-environment interaction analyses are inadequately powered and lack replication due to the small magnitude of interaction effect sizes. Meanwhile, many more potential gene-environment interactions affecting cardiometabolic risk are yet to be discovered. This thesis investigated the role of genetic and environmental factors in a range of cardiometabolic traits (e.g. body mass index (BMI), blood lipids, and blood pressure), using three complementary study designs. <br>
In Paper I, two Swedish cohorts, the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk Study (GLACIER, N=4902) and the Malmö Diet and Cancer Study (MDCS, N=21,824) were analyzed. In the meta-analysis, a nominally significant interaction (Pint=0.03) was observed between sugar sweetened beverage (SSB) intake and a genetic risk score based on BMI related single nucleotide polymorphisms (SNPs). With SSB consumption defined as four categories, one SSB intake category increase was associated with 0.18 kg/m2 mean change of BMI (P= 1.7×10-20; n = 26,726). <br>
In Paper II, interactions between dietary polyunsaturated fatty acid (PUFA) intake and variation at the fatty acid desaturase (FADS) gene cluster were investigated in the GLACIER cohort (N=5,160). In summary, SNP-, haplotype-, and gene-level interaction signals were observed in relation to serum triglyceride concentrations. Through functional annotation, the FADS2 rs5792235 SNP was identified as the probable causal variant in the region (owing to its high functionality score). <br>
In Paper III, using repeated-measures data from &gt;18,000 adults in a subcohort of the Västerbotten Health Survey, an environment-wide association study (EWAS) was performed employing linear mixed-models, assuming different intercepts for each individual. A varying number (12-75) of exposure variables showed environmental-wide-significant associations with nine cardiometabolic traits. For the first time, we showed that heptadecanoic acid (C17:0) is strongly associated with a range of cardiometabolic traits. <br>
In conclusion, in this thesis I report novel and confirmatory evidence of environmental risk factors, as well as gene-environment interactions for major intermediate cardiometabolic risk factors.},
  author       = {Chen, Yan},
  isbn         = {978-91-7619-724-0},
  issn         = {1652-8220},
  language     = {eng},
  number       = {155},
  publisher    = {Lund University: Faculty of Medicine},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Genetic and Environmental Factors in Cardiometabolic Risk},
  url          = {https://lup.lub.lu.se/search/files/56821943/Yan_Chen_web.pdf},
  volume       = {2018},
  year         = {2018},
}