@article {1222, title = {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.}, journal = {Diabetes Care}, volume = {33}, year = {2010}, month = {2010 Dec}, pages = {2684-91}, 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.

}, keywords = {Adult, Aged, Blood Glucose, Edible Grain, European Continental Ancestry Group, Fasting, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Insulin, Male, Middle Aged, Polymorphism, Single Nucleotide}, issn = {1935-5548}, doi = {10.2337/dc10-1150}, author = {Nettleton, Jennifer A and McKeown, Nicola M and Kanoni, Stavroula and Lemaitre, Rozenn N and Hivert, Marie-France and Ngwa, Julius and van Rooij, Frank J A and Sonestedt, Emily and Wojczynski, Mary K and Ye, Zheng and Tanaka, Tosh and Garcia, Melissa and Anderson, Jennifer S and Follis, Jack L and Djouss{\'e}, Luc and Mukamal, Kenneth and Papoutsakis, Constantina and Mozaffarian, Dariush and Zillikens, M Carola and Bandinelli, Stefania and Bennett, Amanda J and Borecki, Ingrid B and Feitosa, Mary F and Ferrucci, Luigi and Forouhi, Nita G and Groves, Christopher J and Hallmans, G{\"o}ran and Harris, Tamara and Hofman, Albert and Houston, Denise K and Hu, Frank B and Johansson, Ingegerd and Kritchevsky, Stephen B and Langenberg, Claudia and Launer, Lenore and Liu, Yongmei and Loos, Ruth J and Nalls, Michael and Orho-Melander, Marju and Renstrom, Frida and Rice, Kenneth and Riserus, Ulf and Rolandsson, Olov and Rotter, Jerome I and Saylor, Georgia and Sijbrands, Eric J G and Sjogren, Per and Smith, Albert and Steingr{\'\i}msd{\'o}ttir, Laufey and Uitterlinden, Andr{\'e} G and Wareham, Nicholas J and Prokopenko, Inga and Pankow, James S and van Duijn, Cornelia M and Florez, Jose C and Witteman, Jacqueline C M and Dupuis, Jos{\'e}e and Dedoussis, George V and Ordovas, Jose M and Ingelsson, Erik and Cupples, L Adrienne and Siscovick, David S and Franks, Paul W and Meigs, James B} } @article {1311, title = {Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.}, journal = {PLoS Genet}, volume = {7}, year = {2011}, month = {2011 Jul}, pages = {e1002193}, abstract = {

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10$^{-}$$^{6}$$^{4}$) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10$^{-}$$^{5}$$^{8}$) and docosapentaenoic acid (DPA, p = 4 x 10$^{-}${\textonesuperior}$^{5}$$^{4}$). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10$^{-}${\textonesuperior}{\texttwosuperior}) and DPA (p = 1 x 10$^{-}$$^{4}${\textthreesuperior}) and lower docosahexaenoic acid (DHA, p = 1 x 10$^{-}${\textonesuperior}$^{5}$). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10$^{-}$$^{8}$). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

}, keywords = {Alleles, Continental Population Groups, Fatty Acids, Omega-3, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1002193}, author = {Lemaitre, Rozenn N and Tanaka, Toshiko and Tang, Weihong and Manichaikul, Ani and Foy, Millennia and Kabagambe, Edmond K and Nettleton, Jennifer A and King, Irena B and Weng, Lu-Chen and Bhattacharya, Sayanti and Bandinelli, Stefania and Bis, Joshua C and Rich, Stephen S and Jacobs, David R and Cherubini, Antonio and McKnight, Barbara and Liang, Shuang and Gu, Xiangjun and Rice, Kenneth and Laurie, Cathy C and Lumley, Thomas and Browning, Brian L and Psaty, Bruce M and Chen, Yii-der I and Friedlander, Yechiel and Djouss{\'e}, Luc and Wu, Jason H Y and Siscovick, David S and Uitterlinden, Andr{\'e} G and Arnett, Donna K and Ferrucci, Luigi and Fornage, Myriam and Tsai, Michael Y and Mozaffarian, Dariush and Steffen, Lyn M} } @article {5880, title = {Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortiu}, journal = {Circ Cardiovasc Genet}, volume = {6}, year = {2013}, month = {2013 Apr}, pages = {171-83}, abstract = {

BACKGROUND- Palmitic acid (16:0), stearic acid (18:0), palmitoleic acid (16:1n-7), and oleic acid (18:1n-9) are major saturated and monounsaturated fatty acids that affect cellular signaling and metabolic pathways. They are synthesized via de novo lipogenesis and are the main saturated and monounsaturated fatty acids in the diet. Levels of these fatty acids have been linked to diseases including type 2 diabetes mellitus and coronary heart disease. METHODS AND RESULTS- Genome-wide association studies were conducted in 5 population-based cohorts comprising 8961 participants of European ancestry to investigate the association of common genetic variation with plasma levels of these 4 fatty acids. We identified polymorphisms in 7 novel loci associated with circulating levels of >=1 of these fatty acids. ALG14 (asparagine-linked glycosylation 14 homolog) polymorphisms were associated with higher 16:0 (P=2.7{\texttimes}10(-11)) and lower 18:0 (P=2.2{\texttimes}10(-18)). FADS1 and FADS2 (desaturases) polymorphisms were associated with higher 16:1n-7 (P=6.6{\texttimes}10(-13)) and 18:1n-9 (P=2.2{\texttimes}10(-32)) and lower 18:0 (P=1.3{\texttimes}10(-20)). LPGAT1 (lysophosphatidylglycerol acyltransferase) polymorphisms were associated with lower 18:0 (P=2.8{\texttimes}10(-9)). GCKR (glucokinase regulator; P=9.8{\texttimes}10(-10)) and HIF1AN (factor inhibiting hypoxia-inducible factor-1; P=5.7{\texttimes}10(-9)) polymorphisms were associated with higher 16:1n-7, whereas PKD2L1 (polycystic kidney disease 2-like 1; P=5.7{\texttimes}10(-15)) and a locus on chromosome 2 (not near known genes) were associated with lower 16:1n-7 (P=4.1{\texttimes}10(-8)). CONCLUSIONS- Our findings provide novel evidence that common variations in genes with diverse functions, including protein-glycosylation, polyunsaturated fatty acid metabolism, phospholipid modeling, and glucose- and oxygen-sensing pathways, are associated with circulating levels of 4 fatty acids in the de novo lipogenesis pathway. These results expand our knowledge of genetic factors relevant to de novo lipogenesis and fatty acid biology.

}, keywords = {Adult, Aged, Chromosomes, Human, Pair 2, Cohort Studies, Coronary Disease, Diabetes Mellitus, Type 2, Fatty Acids, Monounsaturated, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Linkage Disequilibrium, Lipogenesis, Male, Middle Aged, Oleic Acid, Palmitic Acid, Polymorphism, Single Nucleotide, Stearic Acids}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.112.964619}, author = {Wu, Jason H Y and Lemaitre, Rozenn N and Manichaikul, Ani and Guan, Weihua and Tanaka, Toshiko and Foy, Millennia and Kabagambe, Edmond K and Djouss{\'e}, Luc and Siscovick, David and Fretts, Amanda M and Johnson, Catherine and King, Irena B and Psaty, Bruce M and McKnight, Barbara and Rich, Stephen S and Chen, Yii-der I and Nettleton, Jennifer A and Tang, Weihong and Bandinelli, Stefania and Jacobs, David R and Browning, Brian L and Laurie, Cathy C and Gu, Xiangjun and Tsai, Michael Y and Steffen, Lyn M and Ferrucci, Luigi and Fornage, Myriam and Mozaffarian, Dariush} } @article {5879, title = {Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE Consortium Studies.}, journal = {J Nutr}, volume = {143}, year = {2013}, month = {2013 Mar}, pages = {345-53}, abstract = {

Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = -0.009 mmol/L (95\% CI: -0.013, -0.005), P < 0.0001] and insulin [-0.020 ln-pmol/L (95\% CI: -0.024, -0.017), P < 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.

}, keywords = {Blood Glucose, Female, Genetic Loci, Humans, Insulin, Magnesium, Male, Polymorphism, Single Nucleotide, Trace Elements, TRPM Cation Channels}, issn = {1541-6100}, doi = {10.3945/jn.112.172049}, author = {Hruby, Adela and Ngwa, Julius S and Renstrom, Frida and Wojczynski, Mary K and Ganna, Andrea and Hallmans, G{\"o}ran and Houston, Denise K and Jacques, Paul F and Kanoni, Stavroula and Lehtim{\"a}ki, Terho and Lemaitre, Rozenn N and Manichaikul, Ani and North, Kari E and Ntalla, Ioanna and Sonestedt, Emily and Tanaka, Toshiko and van Rooij, Frank J A and Bandinelli, Stefania and Djouss{\'e}, Luc and Grigoriou, Efi and Johansson, Ingegerd and Lohman, Kurt K and Pankow, James S and Raitakari, Olli T and Riserus, Ulf and Yannakoulia, Mary and Zillikens, M Carola and Hassanali, Neelam and Liu, Yongmei and Mozaffarian, Dariush and Papoutsakis, Constantina and Syv{\"a}nen, Ann-Christine and Uitterlinden, Andr{\'e} G and Viikari, Jorma and Groves, Christopher J and Hofman, Albert and Lind, Lars and McCarthy, Mark I and Mikkil{\"a}, Vera and Mukamal, Kenneth and Franco, Oscar H and Borecki, Ingrid B and Cupples, L Adrienne and Dedoussis, George V and Ferrucci, Luigi and Hu, Frank B and Ingelsson, Erik and K{\"a}h{\"o}nen, Mika and Kao, W H Linda and Kritchevsky, Stephen B and Orho-Melander, Marju and Prokopenko, Inga and Rotter, Jerome I and Siscovick, David S and Witteman, Jacqueline C M and Franks, Paul W and Meigs, James B and McKeown, Nicola M and Nettleton, Jennifer A} } @article {6802, title = {Gene {\texttimes} dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.}, journal = {Hum Mol Genet}, volume = {24}, year = {2015}, month = {2015 Aug 15}, pages = {4728-38}, abstract = {

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR~and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

}, keywords = {Adult, Body Mass Index, Case-Control Studies, Diet, Western, Epistasis, Genetic, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Obesity, Polymorphism, Single Nucleotide}, issn = {1460-2083}, doi = {10.1093/hmg/ddv186}, author = {Nettleton, Jennifer A and Follis, Jack L and Ngwa, Julius S and Smith, Caren E and Ahmad, Shafqat and Tanaka, Toshiko and Wojczynski, Mary K and Voortman, Trudy and Lemaitre, Rozenn N and Kristiansson, Kati and Nuotio, Marja-Liisa and Houston, Denise K and Per{\"a}l{\"a}, Mia-Maria and Qi, Qibin and Sonestedt, Emily and Manichaikul, Ani and Kanoni, Stavroula and Ganna, Andrea and Mikkil{\"a}, Vera and North, Kari E and Siscovick, David S and Harald, Kennet and McKeown, Nicola M and Johansson, Ingegerd and Rissanen, Harri and Liu, Yongmei and Lahti, Jari and Hu, Frank B and Bandinelli, Stefania and Rukh, Gull and Rich, Stephen and Booij, Lisanne and Dmitriou, Maria and Ax, Erika and Raitakari, Olli and Mukamal, Kenneth and M{\"a}nnist{\"o}, Satu and Hallmans, G{\"o}ran and Jula, Antti and Ericson, Ulrika and Jacobs, David R and van Rooij, Frank J A and Deloukas, Panos and Sjogren, Per and K{\"a}h{\"o}nen, Mika and Djouss{\'e}, Luc and Perola, Markus and Barroso, In{\^e}s and Hofman, Albert and Stirrups, Kathleen and Viikari, Jorma and Uitterlinden, Andr{\'e} G and Kalafati, Ioanna P and Franco, Oscar H and Mozaffarian, Dariush and Salomaa, Veikko and Borecki, Ingrid B and Knekt, Paul and Kritchevsky, Stephen B and Eriksson, Johan G and Dedoussis, George V and Qi, Lu and Ferrucci, Luigi and Orho-Melander, Marju and Zillikens, M Carola and Ingelsson, Erik and Lehtim{\"a}ki, Terho and Renstrom, Frida and Cupples, L Adrienne and Loos, Ruth J F and Franks, Paul W} }