Genome-Wide Scan for Loci of Adolescent Obesity and Their Relationship with Blood Pressure

Melka, Melkaye G; Bernard, Manon; Mahboubi, Amel; Abrahamowicz, Michał; Paterson, Andrew D.; Syme, Catriona; Lourdusamy, Anbarasu; Schumann, Gunter; Leonard, Gabriel; Perron, Michel; Richer, Louis; Veillette, Suzanne; Gaudet, Daniel; Paus, Tomáš; Pausová, Zdenka

doi:10.1210/jc.2011-1801

Cited by 53 publications

(48 citation statements)

References 19 publications

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“…In the case of BP, neither Freathy et al [25] nor Kring et al [26] observed an association; however, Pausova et al [39] did otherwise with systolic BP in adolescents. Moreover, a recent genome-wide scan identified an association between rs9930333 (SNP in LD with rs9939609) and BP in adolescents [40]. In our study population, the percentage of MS in the obese group was 9.8%, and we did not observe association of any SNPs with MS (data not shown).…”

Section: Discussionmentioning

confidence: 44%

Influence of FTO variants on obesity, inflammation and cardiovascular disease risk biomarkers in Spanish children: a case–control multicentre study

et al. 2013

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BackgroundVariants in the FTO gene have been associated with obesity in children, but this association has not been shown with other biomarkers. We assessed the association of 52 FTO polymorphisms, spanning the whole gene, with obesity and estimated the influence of these polymorphisms on anthropometric, clinical and metabolic parameters as well as inflammation and cardiovascular disease (CVD) risk biomarkers among Spanish children.MethodsA multicentre case–control study was conducted in 534 children (292 obese and 242 with normal-BMI). Anthropometric, clinical, metabolic, inflammation and CVD risk markers were compared using the Student’s t-test for unpaired samples. The genotype relative risk was assessed by comparing the obese and normal-BMI group, calculating the odds ratio. The association of each SNP with phenotypic parameters was analysed using either logistic or linear regression analysis.ResultsAll anthropometric, clinical and metabolic factors as well as inflammatory and CVD risk biomarkers were higher in the obese than in the normal-BMI group, except adiponectin and HDL-c that were lower, and glucose, LDL-c, and metalloproteinase-9 that did not show difference. Four polymorphisms (rs9935401, rs9939609, rs9928094 and rs9930333) were positively associated with obesity and in linkage disequilibrium between each other; the haplotype including the risk alleles of these polymorphisms showed a high risk for obesity. The rs8061518 was negatively associated with obesity and the haplotype including this SNP and rs3826169, rs17818902 and rs7190053 showed a decreased risk for obesity. Additionally, the rs8061518 was associated with weight, diastolic blood pressure, insulin, homeostatic model assessment of insulin resistance, leptin, and active plasminogen inhibitor activator-1 after sex and age adjustment; however, after an additional BMI adjustment, this polymorphism remained associated only with leptin.ConclusionsWe validated the previous reported association of genetic variability in intron 1 of the FTO gene with the risk of obesity and found no association with other related traits in this region of the gene. We have observed strong statistical evidence for an association of rs8061518 in intron 3 of the gene with decreased risk of obesity and low concentration of leptin.

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Section: Discussionmentioning

confidence: 44%

Influence of FTO variants on obesity, inflammation and cardiovascular disease risk biomarkers in Spanish children: a case–control multicentre study

et al. 2013

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“…Genome-wide Association Studies (GWAS) have made significant headway in identifying genetic variants underlying obesity (Cotsapas et al , 2009; Meyre et al , 2009; Jiao et al , 2011; Paternoster et al , 2011; Wang et al , 2011; Melka et al , 2012; Pei et al , 2014; Locke et al , 2015). However, most of these studies focused on body mass index as the main outcome, failing to take into consideration behavioral differences that can precede the development of obesity.…”

Section: Introductionmentioning

confidence: 99%

Gene and environment interaction: Is the differential susceptibility hypothesis relevant for obesity?

Molle

Fatemi

Levitan

et al. 2017

Neuroscience & Biobehavioral Reviews

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The differential susceptibility model states that a given genetic variant is associated with an increased risk of pathology in negative environments but greater than average resilience in enriched ones. While this theory was first implemented in psychiatric-genetic research, it may also help us to unravel the complex ways that genes and environments interact to influence feeding behavior and obesity. We reviewed evidence on gene vs. environment interactions that influence obesity development, aiming to support the applicability of the differential susceptibility model for this condition, and propose that various environmental “layers” relevant for human development should be considered when bearing the differential susceptibility model in mind. Mother-child relationship, socioeconomic status and individual's response are important modifiers of BMI and food intake when interacting with gene variants, “for better and for worse”. While only a few studies to date have investigated obesity outcomes using this approach, we propose that the differential susceptibility hypothesis is in fact highly applicable to the study of genetic and environmental influences on feeding behavior and obesity risk.

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“…The minor alleles of the three SNPs that were nominally associated with a protective role against preeclampsia development in our study have previously been associated with BP regulation [25,26,28]. These SNPs are located in or close to the ATP2B1 , PAX5 , and PLCD3 genes.…”

Section: Discussionmentioning

confidence: 72%

The antihypertensive MTHFR gene polymorphism rs17367504-G is a possible novel protective locus for preeclampsia

Thomsen

McCarthy

Melton

et al. 2017

Journal of Hypertension

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Objective:Preeclampsia is a complex heterogeneous disease commonly defined by new-onset hypertension and proteinuria in pregnancy. Women experiencing preeclampsia have increased risk for cardiovascular diseases (CVD) later in life. Preeclampsia and CVD share risk factors and pathophysiologic mechanisms, including dysregulated inflammation and raised blood pressure. Despite commonalities, little is known about the contribution of shared genes (pleiotropy) to these diseases. This study aimed to investigate whether genetic risk factors for hypertension or inflammation are pleiotropic by also being associated with preeclampsia.Methods:We genotyped 122 single nucleotide polymorphisms (SNPs) in women with preeclampsia (n = 1006) and nonpreeclamptic controls (n = 816) from the Norwegian HUNT Study. SNPs were chosen on the basis of previously reported associations with either nongestational hypertension or inflammation in genome-wide association studies. The SNPs were tested for association with preeclampsia in a multiple logistic regression model.Results:The minor (G) allele of the intronic SNP rs17367504 in the gene methylenetetrahydrofolate reductase (MTHFR) was associated with a protective effect on preeclampsia (odds ratio 0.65, 95% confidence interval 0.53–0.80) in the Norwegian cohort. This association did not replicate in an Australian preeclampsia case–control cohort (P = 0.68, odds ratio 1.05, 95% confidence interval 0.83–1.32, minor allele frequency = 0.15).Conclusion:MTHFR is important for regulating transmethylation processes and is involved in regulation of folate metabolism. The G allele of rs17367504 has previously been shown to protect against nongestational hypertension. Our study suggests a novel association between this allele and reduced risk for preeclampsia. This is the first study associating the minor (G) allele of a SNP within the MTHFR gene with a protective effect on preeclampsia, and in doing so identifying a possible pleiotropic protective effect on preeclampsia and hypertension.

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Genome-Wide Scan for Loci of Adolescent Obesity and Their Relationship with Blood Pressure

Cited by 53 publications

References 19 publications

Influence of FTO variants on obesity, inflammation and cardiovascular disease risk biomarkers in Spanish children: a case–control multicentre study

Influence of FTO variants on obesity, inflammation and cardiovascular disease risk biomarkers in Spanish children: a case–control multicentre study

Gene and environment interaction: Is the differential susceptibility hypothesis relevant for obesity?

The antihypertensive MTHFR gene polymorphism rs17367504-G is a possible novel protective locus for preeclampsia

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