Dataset Information

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

ABSTRACT:

Objective

Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin.

Research design and methods

Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant.

Results

Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele.

Conclusions

Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

SUBMITTER: Nettleton JA

PROVIDER: S-EPMC2992213 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Publications

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

Nettleton Jennifer A JA McKeown Nicola M NM Kanoni Stavroula S Lemaitre Rozenn N RN Hivert Marie-France MF Ngwa Julius J van Rooij Frank J A FJ Sonestedt Emily E Wojczynski Mary K MK Ye Zheng Z Tanaka Tosh T Garcia Melissa M Anderson Jennifer S JS Follis Jack L JL Djousse Luc L Mukamal Kenneth K Papoutsakis Constantina C Mozaffarian Dariush D Zillikens M Carola MC Bandinelli Stefania S Bennett Amanda J AJ Borecki Ingrid B IB Feitosa Mary F MF Ferrucci Luigi L Forouhi Nita G NG Groves Christopher J CJ Hallmans Goran G Harris Tamara T Hofman Albert A Houston Denise K DK Hu Frank B FB Johansson Ingegerd I Kritchevsky Stephen B SB Langenberg Claudia C Launer Lenore L Liu Yongmei Y Loos Ruth J RJ Nalls Michael M Orho-Melander Marju M Renstrom Frida F Rice Kenneth K Riserus Ulf U Rolandsson Olov O Rotter Jerome I JI Saylor Georgia G Sijbrands Eric J G EJ Sjogren Per P Smith Albert A Steingrímsdóttir Laufey L Uitterlinden André G AG Wareham Nicholas J NJ Prokopenko Inga I Pankow James S JS van Duijn Cornelia M CM Florez Jose C JC Witteman Jacqueline C M JC Dupuis Josée J Dedoussis George V GV Ordovas Jose M JM Ingelsson Erik E Cupples L Adrienne L Siscovick David S DS Franks Paul W PW Meigs James B JB

Diabetes care 20100806 12

<h4>Objective</h4>Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin.<h4 ...[more]

PMID: 20693352

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Project description:ImportanceIndividuals of African descent have been reported to be at higher risk for becoming visually impaired from glaucoma compared with individuals of European descent.ObjectiveTo investigate racial differences in longitudinal visual field variability and their impact on time to detect visual field progression.Design, setting, and participantsThis multicenter prospective observational cohort study included 236 eyes of 173 individuals of European descent and 235 eyes of 171 individuals of African descent followed up for a mean (SD) time of 7.5 (3.4) years.Main outcomes and measuresDifferences in test-retest variability and simulated time to detect progression in individuals of African descent and of European descent with glaucoma. Standard automated perimetry mean deviation values were regressed over time for each eye, and SD of the residuals was used as a measure of variability. Distributions of residuals were used in computer simulations to reconstruct "real-world" standard automated perimetry mean deviation trajectories under different assumptions about rate of change and frequency of testing. Times to detect progression were obtained for the simulated visual fields.ResultsAmong the 344 patients, the mean (SD) age at baseline was 60.2 (10.0) and 60.6 (9.0) years for individuals of African descent and of European descent, respectively; 94 (52%) and 86 (48%) of individuals of African descent and of European descent were women, respectively. The mean SD of the residuals was larger in eyes of individuals of African descent vs those of European descent (1.45 [0.83] dB vs 1.12 [0.48] dB; mean difference: 0.33 dB; 95% CI of the difference, 0.21-0.46; P < .001). The eyes in individuals of African descent had a larger increase in variability with worsening disease (P < .001). When simulations were performed assuming common progression scenarios, there was a delay to detect progression in eyes of individuals of African descent compared with those of European descent. For a scenario with baseline mean deviation of -10 dB and rate of change of -0.5 dB/y, detection of progression in individuals of African descent was delayed by 3.1 (95% CI, 2.9-3.2) years, when considered 80% power and annual tests.Conclusions and relevancePatients of African descent with glaucoma showed increased visual field variability compared with those of European descent, resulting in delayed detection of progression that may contribute to explain higher rates of glaucoma-related visual impairment in individuals of African descent compared with those of European descent with glaucoma.

Project description:OBJECTIVES:We have previously reported a top-ranked risk gene [i.e., serine incorporator 2 gene (SERINC2)] for alcohol dependence in individuals of European descent by analyzing the common variants in a genome-wide association study. In the present study, we comprehensively examined the rare variants [minor allele frequency (MAF)<0.05] in the NKAIN1-SERINC2 region to confirm our previous finding. MATERIALS AND METHODS:A discovery sample (1409 European-American patients with alcohol dependence and 1518 European-American controls) and a replication sample (6438 European-Australian family participants with 1645 alcohol-dependent probands) were subjected to an association analysis. A total of 39,903 individuals from 19 other cohorts with 11 different neuropsychiatric and neurological disorders served as contrast groups. The entire NKAIN1-SERINC2 region was imputed in all cohorts using the same reference panels of genotypes that included rare variants from the whole-genome sequencing data. We stringently cleaned the phenotype and genotype data, and obtained a total of about 220 single-nucleotide polymorphisms in individuals of European descent and about 450 single-nucleotide polymorphisms in the individuals of African descent with 0<MAF<0.05 for an association analysis. RESULTS:Using a weighted regression analysis implemented in the program SCORE-Seq, we found a rare variant constellation across the entire NKAIN1-SERINC2 region that was associated with alcohol dependence in European-Americans (Fp: overall, P=1.8×10(-4); VT: overall, P=1.4×10(-4); Collapsing, P=6.5×10(-5)) and European-Australians (Fp: overall, P=0.028; Collapsing, P=0.025), but not in African-Americans, and not associated with any other disorder examined. Association signals in this region came mainly from SERINC2, a gene that codes for an activity-regulated protein expressed in the brain that incorporates serine into lipids. In addition, 26 individual rare variants were nominally associated with alcohol dependence in European-Americans (P<0.05). The associations of five of these rare variants that lay within SERINC2 showed region-wide significance (P<?=0.0006) and 25 associations survived correction for a false discovery rate (q<0.05). The associations of two rare variants at SERINC2 were replicated in European-Australians (P<0.05). CONCLUSION:We concluded that SERINC2 was a replicable and significant risk gene specific for alcohol dependence in individuals of European descent.

Dataset Information

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

Objective

Research design and methods

Results

Conclusions

Publications

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

Similar Datasets

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