Population-specific coding variant underlies genome-wide association with adiponectin level

Croteau‐Chonka, Damien C.; Wu, Ying; Li, Yun; Fogarty, Marie P.; Lange, Leslie A.; Kuzawa, Christopher W.; McDade, Thomas W.; Borja, Judith B.; Luo, Jingchun; AbdelBaky, Omar; Combs, Terry P.; Adair, Linda S.; Lange, Ethan M.; Mohlke, Karen L.

doi:10.1093/hmg/ddr480

Cited by 41 publications

(40 citation statements)

References 46 publications

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“…Top SNPs in these studies were consistent with top SNPs in our study, although it should be noted that two of the studies were previously performed in the InCHIANTI population, which was also included in this analysis. Ultimately, haplotype analyses with denser SNP panels, direct sequencing and functional analyses will be required to localize the causal variants in this region (38). …”

Section: Discussionmentioning

confidence: 99%

Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults

Matteini¹,

Lange

et al. 2014

Cytokine

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Activation of inflammatory pathways measured by serum inflammatory markers such as interleukin-18 (IL-18) and interleukin-1 receptor antagonist (IL-1ra) is strongly associated with the progression of chronic disease states in older adults. Given that these serum cytokine levels are in part a heritable trait, genetic variation may predict increased serum levels. Using the Cardiovascular Health Study and InCHIANTI cohorts, a genome-wide association study was performed to identify genetic variants that influence IL18 and IL-1ra serum levels among older adults. Multiple linear regression models characterized the association between each SNP and log-transformed cytokine values. Tests for multiple independent signals within statistically significant loci were performed using haplotype analysis and regression models conditional on lead SNP in each region. Multiple SNPs were associated with these cytokines with genome-wide significance, including SNPs in the IL18-BCO gene region of chromosome 2 for IL-18 (top SNP rs2250417, P = 1.9×10−32) and in the IL1 gene family region of chromosome 2 for IL-1ra (rs6743376, P = 2.3×10−26). Haplotype tests and conditional linear regression models showed evidence of multiple independent signals in these regions. Serum IL-18 levels were also associated with a region on chromosome 2 containing the NLRC4 gene (rs12989936, P = 2.7×10−19). These data characterize multiple robust genetic signals that influence IL-18 and IL-1ra cytokine production. In particular, the signal for serum IL-18 located on chromosome two is novel and potentially important in inflammasome triggered chronic activation of inflammation in older adults. Replication in independent cohorts is an important next step, as well as molecular studies to better understand the role of NLRC4.

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Section: Discussionmentioning

confidence: 99%

Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults

Matteini¹,

Lange

et al. 2014

Cytokine

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“…The genotyping and quality control of Metabochip SNPs in the CLHNS offspring were described previously ( 31 ).…”

Section: Genotyping and Imputationmentioning

confidence: 99%

Genetic association with lipids in Filipinos: waist circumference modifies an APOA5 effect on triglyceride levels

Marvelle

et al. 2013

Journal of Lipid Research

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“…None of the receptor SNPs was associated with serum adiponectin in this study [27]. Furthermore, rare population-specific mutations have been shown to account for ~17% of the variance in serum adiponectin concentrations ( Table 1) [28][29].…”

Section: Adiponectin (Adipoq)mentioning

confidence: 58%

“…However, this would be rather an indirect/downstream effect on serum leptin levels than an effect of polymorphisms directly acting on LEP gene transcription and protein expression, and the hypothesis is not yet proven. In contrast, in a recent but small study, [23], [28], rev. …”

Section: Leptin (Lep)mentioning

confidence: 78%

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Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

Schleinitz¹

2016

Rev Diabet Stud

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■ AbstractAdipose tissue secretes an abundance of proteins. Some of these proteins are known as adipokines and adipose-derived hormones which have been linked with metabolic disorders, including type 2 diabetes, and even with cancer. Variance in serum adipokine concentration is often closely associated with an increase (obesity) or decrease (lipodystrophy) in fat tissue mass, and it is affected by age, gender, and localization of the adipose tissue. However, there may be genetic variants which, in consequence, influence the serum concentration of a certain adipokine, and thereby promote metabolic disturbances or, with regard to the "protective" allele, exert beneficial effects. This review focuses on the genetic determination of serum levels of the following adipokines: adiponectin, chemerin, leptin, progranulin, resistin, retinol binding protein 4, vaspin, adipsin, apelin, and omentin. The article reports on the latest findings from genome-wide association studies (GWAS) and candidate gene studies, showing variants located in/nearby the adipokine genes and other (non-receptor) genes. An extra chapter highlights adipokine-receptor variants. Epigenetic studies on adipokines are also addressed.

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Population-specific coding variant underlies genome-wide association with adiponectin level

Cited by 41 publications

References 46 publications

Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults

Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults

Genetic association with lipids in Filipinos: waist circumference modifies an APOA5 effect on triglyceride levels

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

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