Adipose Co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes

Haas, Blake E.; Horvath, Steve; Pietiläinen, Kirsi H.; Cantor, Rita M.; Nikkola, Elina; Weissglas‐Volkov, Daphna; Rissanen, Aila; Civelek, Mete; Cruz-Bautista, Ivette; Riba, Laura; Kuusisto, Johanna; Kaprio, Jaakko; Tusié-Luna, Teresa; Laakso, Markku; Aguilar-Salinas, Carlos A.; Pajukanta, Päivi

doi:10.1186/1755-8794-5-61

Cited by 35 publications

(26 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, HOXA5 is up-regulated in abdominal subcutaneous adipose tissue following fat loss (one year after bariatric surgery) [68]. In addition, nominal associations were seen between either waist circumference or BMI and DNA methylation within several other genes previously implicated in serum triglyceride levels ( ARHGAP9 [69]); obesity and adipogenesis ( CDKN2A ( p16 ) [70], [71], FRZB [72], JAK3 [73], PEG3 [74]); and glucose homeostasis and insulin resistance ( CDKN2A [75]–[77], SMARCB1 [78]). …”

Section: Resultsmentioning

confidence: 98%

Genetic Effects on DNA Methylation and Its Potential Relevance for Obesity in Mexican Americans

et al. 2013

View full text Add to dashboard Cite

Several studies have identified effects of genetic variation on DNA methylation patterns and associated heritability, with research primarily focused on Caucasian individuals. In this paper, we examine the evidence for genetic effects on DNA methylation in a Mexican American cohort, a population burdened by a high prevalence of obesity. Using an Illumina-based platform and following stringent quality control procedures, we assessed a total of 395 CpG sites in peripheral blood samples obtained from 183 Mexican American individuals for evidence of heritability, proximal genetic regulation and association with age, sex and obesity measures (i.e. waist circumference and body mass index). We identified 16 CpG sites (∼4%) that were significantly heritable after Bonferroni correction for multiple testing and 27 CpG sites (∼6.9%) that showed evidence of genetic effects. Six CpG sites (∼2%) were associated with age, primarily exhibiting positive relationships, including CpG sites in two genes that have been implicated in previous genome-wide methylation studies of age (FZD9 and MYOD1). In addition, we identified significant associations between three CpG sites (∼1%) and sex, including DNA methylation in CASP6, a gene that may respond to estradiol treatment, and in HSD17B12, which encodes a sex steroid hormone. Although we did not identify any significant associations between DNA methylation and the obesity measures, several nominally significant results were observed in genes related to adipogenesis, obesity, energy homeostasis and glucose homeostasis (ARHGAP9, CDKN2A, FRZB, HOXA5, JAK3, MEST, NPY, PEG3 and SMARCB1). In conclusion, we were able to replicate several findings from previous studies in our Mexican American cohort, supporting an important role for genetic effects on DNA methylation. In addition, we found a significant influence of age and sex on DNA methylation, and report on trend-level, novel associations between DNA methylation and measures of obesity.

show abstract

Section: Resultsmentioning

confidence: 98%

Genetic Effects on DNA Methylation and Its Potential Relevance for Obesity in Mexican Americans

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The gene set (ARHGAP30, USF1) identified on BTA3 showed an important effect on the control of several genes related to lipid and glucose metabolism 61,62 . Hence, these genes can cause variation in AFC in Nellore heifers due to their influence on metabolic homeostasis, by direct action on the reproductive process, e.g.…”

Section: Shared Regions Surround Genes For Afc On Medium and High Ec mentioning

confidence: 99%

Genome-wide scan highlights the role of candidate genes on phenotypic plasticity for age at first calving in Nellore heifers

Mota

Lopes²,

Júnior

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Age at first calving (AFC) plays an important role in the economic efficiency of beef cattle production. This trait can be affected by a combination of genetic and environmental factors, leading to physiological changes in response to heifers' adaptation to a wide range of environments. Genomewide association studies through the reaction norm model were carried out to identify genomic regions associated with AFC in Nellore heifers, raised under different environmental conditions (EC). The SNP effects for AFC were estimated in three EC levels (Low, Medium, and High, corresponding to average contemporary group effects on yearling body weight equal to 159.40, 228.6 and 297.6 kg, respectively), which unraveled shared and unique genomic regions for AFC in Low, Medium, and High EC levels, that varied according to the genetic correlation between AFC in different EC levels. The significant genomic regions harbored key genes that might play an important biological role in controlling hormone signaling and metabolism. Shared genomic regions among EC levels were identified on BTA 2 and 14, harboring candidate genes associated with energy metabolism (IGFBP2, IGFBP5, SHOX, SMARCAL1, LYN, RPS20, MOS, PLAG1, CHCD7, and SDR16C6). Gene set enrichment analyses identified important biological functions related to growth, hormone levels affecting female fertility, physiological processes involved in female pregnancy, gamete generation, ovulation cycle, and age at puberty. the genomic regions highlighted differences in the physiological processes linked to AFC in different EC levels and metabolic processes that support complex interactions between the gonadotropic axes and sexual precocity in nellore heifers. open Scientific RepoRtS | (2020) 10:6481 | https://doi.org/10.1038/s41598-020-63516-4 www.nature.com/scientificreports www.nature.com/scientificreports/ pathway and gene network analyses from these results can be performed to uncover mechanisms whereby the environment can potentially affect the sexual precocity in cattle. Such knowledge regarding genomic regions and biological pathways involved with GxE interactions in Nellore heifers' sexual precocity is important to identify molecular mechanisms underlying the phenotypic responses to different environments. Hence, this study was carried out to evaluate the changes in the SNP effect estimates, as well as the biological processes associated with age at first calving in three environmental conditions, combining RN models and GWAS. Materials and Methodsethics approval. The animal procedures in this study were approved by Animal Care of the São Paulo State University (UNESP), School of Agricultural and Veterinary Science Ethical Committee (protocol number 18.340/16). All the data sampling was performed in accordance with CEUA/ FCAV-UNESP guidelines and regulations.phenotypic and genotypic data. Age at first calving (AFC) records were obtained from 185,356Nellore heifers belonging to three commercial breeding programs (DeltaGen, Paint -CRV Lagoa and Cia de Melhoramento), which are p...

show abstract

“…The interaction on LDL-C was between rs2247056 and rs1030431 ( P c = 0.03 after Bonferroni correction). Both rs2247056 and rs1030431 were marginally associated with LDL-C, TG, and TC [7,38]. We then performed fine mapping analysis in the two loci surrounding the two SNPs to find the most significant interaction to be between rs2853928 and rs1993453 ( P c = 0.01).…”

Section: Methods and Resultsmentioning

confidence: 99%

Biological Knowledge-Driven Analysis of Epistasis in Human GWAS with Application to Lipid Traits

Keinan

Clark

2014

Methods in Molecular Biology

View full text Add to dashboard Cite

While the importance of epistasis is well established, specific gene-gene interactions have rarely been identified in human genome-wide association studies (GWAS), mainly due to the low power associated with such interaction tests. In this chapter, we integrate biological knowledge and human GWAS data to reveal epistatic interactions underlying quantitative lipid traits which are major risk factors for coronary artery disease. To increase power to detect interactions, we only tested pairs of SNPs filtered by prior biological knowledge, including GWAS results, protein-protein interactions, and pathway information. Using published GWAS results and 9,713 European Americans (EA) from the Atherosclerosis Risk in Communities (ARIC) study, we identified an interaction between HMGCR and LIPC affecting high-density lipoprotein cholesterol (HDL-C) levels. We then validated this interaction in additional EA cohorts from the Framingham Heart Study and the Multi-Ethnic Study of Atherosclerosis (MESA). We also validated the interaction in the ARIC African American sample and in the Hispanic American sample from MESA. Both HMGCR and LIPC are involved in the metabolism of lipid and lipoproteins, and LIPC itself has been associated with HDL-C. Moreover, the interaction affects HDL-C twice as much as the marginal effect of LIPC, with the effect of the two genes and their interaction combined explaining 0.8% of the variation in HDL. These results suggest the potential of the biological knowledge-driven approach to detect epistatic interactions in human GWAS, which may hold the key to exploring the role gene-gene interactions play in connecting genotype and phenotype in current and future genetic association studies.

show abstract

Adipose Co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes

Cited by 35 publications

References 30 publications

Genetic Effects on DNA Methylation and Its Potential Relevance for Obesity in Mexican Americans

Genetic Effects on DNA Methylation and Its Potential Relevance for Obesity in Mexican Americans

Genome-wide scan highlights the role of candidate genes on phenotypic plasticity for age at first calving in Nellore heifers

Biological Knowledge-Driven Analysis of Epistasis in Human GWAS with Application to Lipid Traits

Contact Info

Product

Resources

About