@article {6270, title = {Sleep duration does not mediate or modify association of common genetic variants with type 2 diabetes.}, journal = {Diabetologia}, volume = {57}, year = {2014}, month = {2014 Feb}, pages = {339-46}, abstract = {

AIMS/HYPOTHESIS: Short and long sleep duration are associated with increased risk of type 2 diabetes. We aimed to investigate whether genetic variants for fasting glucose or type 2 diabetes associate with short or long sleep duration and whether sleep duration modifies the association of genetic variants with these traits.

METHODS: We examined the cross-sectional relationship between self-reported habitual sleep duration and prevalence of type 2 diabetes in individuals of European descent participating in five studies included in the Candidate Gene Association Resource (CARe), totalling 1,474 cases and 8,323 controls. We tested for association of 16 fasting glucose-associated variants, 27 type 2 diabetes-associated variants and aggregate genetic risk scores with continuous and dichotomised (<=5~h or >=9~h) sleep duration using regression models adjusted for age, sex and BMI. Finally, we tested whether a gene {\texttimes} behaviour interaction of variants with sleep duration had an impact on fasting glucose or type 2 diabetes risk.

RESULTS: Short sleep duration was significantly associated with type 2 diabetes in CARe (OR 1.32; 95\% CI 1.08, 1.61; p = 0.008). Variants previously associated with fasting glucose or type 2 diabetes and genetic risk scores were not associated with sleep duration. Furthermore, no study-wide significant interaction was observed between sleep duration and these variants on glycaemic traits. Nominal interactions were observed for sleep duration and PPARG rs1801282, CRY2 rs7943320 and HNF1B rs4430796 in influencing risk of type 2 diabetes (p < 0.05).

CONCLUSIONS/INTERPRETATION: Our findings suggest that differences in habitual sleep duration do not mediate or modify the relationship between common variants underlying glycaemic traits (including in circadian rhythm genes) and diabetes.

}, keywords = {Blood Glucose, Body Composition, Body Mass Index, Cross-Sectional Studies, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Fasting, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Glucose Intolerance, Glycated Hemoglobin A, Humans, Insulin Resistance, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Sleep, Surveys and Questionnaires, Time Factors, United States}, issn = {1432-0428}, doi = {10.1007/s00125-013-3110-y}, author = {Tare, Archana and Lane, Jacqueline M and Cade, Brian E and Grant, Struan F A and Chen, Ting-Hsu and Punjabi, Naresh M and Lauderdale, Diane S and Zee, Phyllis C and Gharib, Sina A and Gottlieb, Daniel J and Scheer, Frank A J L and Redline, Susan and Saxena, Richa} } @article {7147, title = {Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits.}, journal = {Aging Cell}, volume = {15}, year = {2016}, month = {2016 Oct}, pages = {811-24}, abstract = {

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30~884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype-phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90~years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci.

}, issn = {1474-9726}, doi = {10.1111/acel.12490}, author = {Teumer, Alexander and Qi, Qibin and Nethander, Maria and Aschard, Hugues and Bandinelli, Stefania and Beekman, Marian and Berndt, Sonja I and Bidlingmaier, Martin and Broer, Linda and Cappola, Anne and Ceda, Gian Paolo and Chanock, Stephen and Chen, Ming-Huei and Chen, Tai C and Chen, Yii-Der Ida and Chung, Jonathan and Del Greco Miglianico, Fabiola and Eriksson, Joel and Ferrucci, Luigi and Friedrich, Nele and Gnewuch, Carsten and Goodarzi, Mark O and Grarup, Niels and Guo, Tingwei and Hammer, Elke and Hayes, Richard B and Hicks, Andrew A and Hofman, Albert and Houwing-Duistermaat, Jeanine J and Hu, Frank and Hunter, David J and Husemoen, Lise L and Isaacs, Aaron and Jacobs, Kevin B and Janssen, Joop A M J L and Jansson, John-Olov and Jehmlich, Nico and Johnson, Simon and Juul, Anders and Karlsson, Magnus and Kilpel{\"a}inen, Tuomas O and Kovacs, Peter and Kraft, Peter and Li, Chao and Linneberg, Allan and Liu, Yongmei and Loos, Ruth J F and Lorentzon, Mattias and Lu, Yingchang and Maggio, Marcello and M{\"a}gi, Reedik and Meigs, James and Mellstr{\"o}m, Dan and Nauck, Matthias and Newman, Anne B and Pollak, Michael N and Pramstaller, Peter P and Prokopenko, Inga and Psaty, Bruce M and Reincke, Martin and Rimm, Eric B and Rotter, Jerome I and Saint Pierre, Aude and Schurmann, Claudia and Seshadri, Sudha and Sj{\"o}gren, Klara and Slagboom, P Eline and Strickler, Howard D and Stumvoll, Michael and Suh, Yousin and Sun, Qi and Zhang, Cuilin and Svensson, Johan and Tanaka, Toshiko and Tare, Archana and T{\"o}njes, Anke and Uh, Hae-Won and van Duijn, Cornelia M and van Heemst, Diana and Vandenput, Liesbeth and Vasan, Ramachandran S and V{\"o}lker, Uwe and Willems, Sara M and Ohlsson, Claes and Wallaschofski, Henri and Kaplan, Robert C} }