@article {6844, title = {Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians.}, journal = {Am J Clin Nutr}, volume = {102}, year = {2015}, month = {2015 Nov}, pages = {1266-78}, abstract = {

BACKGROUND: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown.

OBJECTIVE: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus.

DESIGN: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations.

RESULTS: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95\% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95\% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-ln-pmol/L (95\% CI: 0.035, 0.063-ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance.

CONCLUSION: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms. Six of the participating studies are registered at clinicaltrials.gov as NCT0000513 (Atherosclerosis Risk in Communities), NCT00149435 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetics of Lipid Lowering Drugs and Diet Network), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

}, keywords = {Blood Glucose, Cohort Studies, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hyperglycemia, Hyperinsulinism, Insulin, Insulin Resistance, Insulin-Secreting Cells, Meat, Meat Products, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors}, issn = {1938-3207}, doi = {10.3945/ajcn.114.101238}, author = {Fretts, Amanda M and Follis, Jack L and Nettleton, Jennifer A and Lemaitre, Rozenn N and Ngwa, Julius S and Wojczynski, Mary K and Kalafati, Ioanna Panagiota and Varga, Tibor V and Frazier-Wood, Alexis C and Houston, Denise K and Lahti, Jari and Ericson, Ulrika and van den Hooven, Edith H and Mikkil{\"a}, Vera and Kiefte-de Jong, Jessica C and Mozaffarian, Dariush and Rice, Kenneth and Renstrom, Frida and North, Kari E and McKeown, Nicola M and Feitosa, Mary F and Kanoni, Stavroula and Smith, Caren E and Garcia, Melissa E and Tiainen, Anna-Maija and Sonestedt, Emily and Manichaikul, Ani and van Rooij, Frank J A and Dimitriou, Maria and Raitakari, Olli and Pankow, James S and Djouss{\'e}, Luc and Province, Michael A and Hu, Frank B and Lai, Chao-Qiang and Keller, Margaux F and Per{\"a}l{\"a}, Mia-Maria and Rotter, Jerome I and Hofman, Albert and Graff, Misa and K{\"a}h{\"o}nen, Mika and Mukamal, Kenneth and Johansson, Ingegerd and Ordovas, Jose M and Liu, Yongmei and M{\"a}nnist{\"o}, Satu and Uitterlinden, Andr{\'e} G and Deloukas, Panos and Sepp{\"a}l{\"a}, Ilkka and Psaty, Bruce M and Cupples, L Adrienne and Borecki, Ingrid B and Franks, Paul W and Arnett, Donna K and Nalls, Mike A and Eriksson, Johan G and Orho-Melander, Marju and Franco, Oscar H and Lehtim{\"a}ki, Terho and Dedoussis, George V and Meigs, James B and Siscovick, David S} } @article {6614, title = {Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants.}, journal = {Am J Clin Nutr}, volume = {101}, year = {2015}, month = {2015 Jan}, pages = {135-43}, abstract = {

BACKGROUND: Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake.

OBJECTIVES: We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations.

DESIGN: We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.

RESULTS: We observed a significant association between sleep duration and lower BMI (β {\textpm} SE = 0.16 {\textpm} 0.04, P < 0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 {\textpm} 0.06\%, P = 0.03; women: 0.10 {\textpm} 0.05\%, P = 0.04) and with lower carbohydrate (-0.31 {\textpm} 0.12\%, P < 0.01), higher total fat (0.18 {\textpm} 0.09\%, P = 0.05), and higher PUFA (0.05 {\textpm} 0.02\%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake.

CONCLUSIONS: Our results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile.

}, keywords = {Adult, Body Mass Index, CLOCK Proteins, Cohort Studies, Cross-Sectional Studies, Diet, Dietary Proteins, Energy Intake, European Continental Ancestry Group, Fatty Acids, Unsaturated, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Obesity, Polymorphism, Single Nucleotide, Sleep, Young Adult}, issn = {1938-3207}, doi = {10.3945/ajcn.114.095026}, author = {Dashti, Hassan S and Follis, Jack L and Smith, Caren E and Tanaka, Toshiko and Cade, Brian E and Gottlieb, Daniel J and Hruby, Adela and Jacques, Paul F and Lamon-Fava, Stefania and Richardson, Kris and Saxena, Richa and Scheer, Frank A J L and Kovanen, Leena and Bartz, Traci M and Per{\"a}l{\"a}, Mia-Maria and Jonsson, Anna and Frazier-Wood, Alexis C and Kalafati, Ioanna-Panagiota and Mikkil{\"a}, Vera and Partonen, Timo and Lemaitre, Rozenn N and Lahti, Jari and Hernandez, Dena G and Toft, Ulla and Johnson, W Craig and Kanoni, Stavroula and Raitakari, Olli T and Perola, Markus and Psaty, Bruce M and Ferrucci, Luigi and Grarup, Niels and Highland, Heather M and Rallidis, Loukianos and K{\"a}h{\"o}nen, Mika and Havulinna, Aki S and Siscovick, David S and R{\"a}ikk{\"o}nen, Katri and J{\o}rgensen, Torben and Rotter, Jerome I and Deloukas, Panos and Viikari, Jorma S A and Mozaffarian, Dariush and Linneberg, Allan and Sepp{\"a}l{\"a}, Ilkka and Hansen, Torben and Salomaa, Veikko and Gharib, Sina A and Eriksson, Johan G and Bandinelli, Stefania and Pedersen, Oluf and Rich, Stephen S and Dedoussis, George and Lehtim{\"a}ki, Terho and Ordovas, Jose M} } @article {7588, title = {Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent.}, journal = {Mol Nutr Food Res}, year = {2017}, month = {2017 Sep 21}, abstract = {

SCOPE: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption.

METHODS AND RESULTS: A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction <10-7) , and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3{\textquoteright} of LINC00333) was replicated (p-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p-interaction = 7.36 {\texttimes} 10-8) such that each serving of low-fat dairy was associated with 0.225 kg m-2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure.

CONCLUSION: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.

}, issn = {1613-4133}, doi = {10.1002/mnfr.201700347}, author = {Smith, Caren E and Follis, Jack L and Dashti, Hassan S and Tanaka, Toshiko and Graff, Mariaelisa and Fretts, Amanda M and Kilpel{\"a}inen, Tuomas O and Wojczynski, Mary K and Richardson, Kris and Nalls, Mike A and Schulz, Christina-Alexandra and Liu, Yongmei and Frazier-Wood, Alexis C and van Eekelen, Esther and Wang, Carol and de Vries, Paul S and Mikkil{\"a}, Vera and Rohde, Rebecca and Psaty, Bruce M and Hansen, Torben and Feitosa, Mary F and Lai, Chao-Qiang and Houston, Denise K and Ferruci, Luigi and Ericson, Ulrika and Wang, Zhe and de Mutsert, Ren{\'e}e and Oddy, Wendy H and de Jonge, Ester A L and Sepp{\"a}l{\"a}, Ilkka and Justice, Anne E and Lemaitre, Rozenn N and S{\o}rensen, Thorkild I A and Province, Michael A and Parnell, Laurence D and Garcia, Melissa E and Bandinelli, Stefania and Orho-Melander, Marju and Rich, Stephen S and Rosendaal, Frits R and Pennell, Craig E and Kiefte-de Jong, Jessica C and K{\"a}h{\"o}nen, Mika and Young, Kristin L and Pedersen, Oluf and Aslibekyan, Stella and Rotter, Jerome I and Mook-Kanamori, Dennis O and Zillikens, M Carola and Raitakari, Olli T and North, Kari E and Overvad, Kim and Arnett, Donna K and Hofman, Albert and Lehtim{\"a}ki, Terho and Tj{\o}nneland, Anne and Uitterlinden, Andr{\'e} G and Rivadeneira, Fernando and Franco, Oscar H and German, J Bruce and Siscovick, David S and Cupples, L Adrienne and Ordovas, Jose M} } @article {7568, title = {Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {2017 Oct 13}, pages = {910}, abstract = {

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents{\textquoteright} survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

}, issn = {2041-1723}, doi = {10.1038/s41467-017-00934-5}, author = {Joshi, Peter K and Pirastu, Nicola and Kentistou, Katherine A and Fischer, Krista and Hofer, Edith and Schraut, Katharina E and Clark, David W and Nutile, Teresa and Barnes, Catriona L K and Timmers, Paul R H J and Shen, Xia and Gandin, Ilaria and McDaid, Aaron F and Hansen, Thomas Folkmann and Gordon, Scott D and Giulianini, Franco and Boutin, Thibaud S and Abdellaoui, Abdel and Zhao, Wei and Medina-G{\'o}mez, Carolina and Bartz, Traci M and Trompet, Stella and Lange, Leslie A and Raffield, Laura and van der Spek, Ashley and Galesloot, Tessel E and Proitsi, Petroula and Yanek, Lisa R and Bielak, Lawrence F and Payton, Antony and Murgia, Federico and Concas, Maria Pina and Biino, Ginevra and Tajuddin, Salman M and Sepp{\"a}l{\"a}, Ilkka and Amin, Najaf and Boerwinkle, Eric and B{\o}rglum, Anders D and Campbell, Archie and Demerath, Ellen W and Demuth, Ilja and Faul, Jessica D and Ford, Ian and Gialluisi, Alessandro and G{\"o}gele, Martin and Graff, Mariaelisa and Hingorani, Aroon and Hottenga, Jouke-Jan and Hougaard, David M and Hurme, Mikko A and Ikram, M Arfan and Jylh{\"a}, Marja and Kuh, Diana and Ligthart, Lannie and Lill, Christina M and Lindenberger, Ulman and Lumley, Thomas and M{\"a}gi, Reedik and Marques-Vidal, Pedro and Medland, Sarah E and Milani, Lili and Nagy, Reka and Ollier, William E R and Peyser, Patricia A and Pramstaller, Peter P and Ridker, Paul M and Rivadeneira, Fernando and Ruggiero, Daniela and Saba, Yasaman and Schmidt, Reinhold and Schmidt, Helena and Slagboom, P Eline and Smith, Blair H and Smith, Jennifer A and Sotoodehnia, Nona and Steinhagen-Thiessen, Elisabeth and van Rooij, Frank J A and Verbeek, Andr{\'e} L and Vermeulen, Sita H and Vollenweider, Peter and Wang, Yunpeng and Werge, Thomas and Whitfield, John B and Zonderman, Alan B and Lehtim{\"a}ki, Terho and Evans, Michele K and Pirastu, Mario and Fuchsberger, Christian and Bertram, Lars and Pendleton, Neil and Kardia, Sharon L R and Ciullo, Marina and Becker, Diane M and Wong, Andrew and Psaty, Bruce M and van Duijn, Cornelia M and Wilson, James G and Jukema, J Wouter and Kiemeney, Lambertus and Uitterlinden, Andr{\'e} G and Franceschini, Nora and North, Kari E and Weir, David R and Metspalu, Andres and Boomsma, Dorret I and Hayward, Caroline and Chasman, Daniel and Martin, Nicholas G and Sattar, Naveed and Campbell, Harry and Esko, T{\~o}nu and Kutalik, Zolt{\'a}n and Wilson, James F} } @article {7396, title = {Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation.}, journal = {Nat Genet}, volume = {49}, year = {2017}, month = {2017 Jun}, pages = {946-952}, abstract = {

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.

}, issn = {1546-1718}, doi = {10.1038/ng.3843}, author = {Christophersen, Ingrid E and Rienstra, Michiel and Roselli, Carolina and Yin, Xiaoyan and Geelhoed, Bastiaan and Barnard, John and Lin, Honghuang and Arking, Dan E and Smith, Albert V and Albert, Christine M and Chaffin, Mark and Tucker, Nathan R and Li, Molong and Klarin, Derek and Bihlmeyer, Nathan A and Low, Siew-Kee and Weeke, Peter E and M{\"u}ller-Nurasyid, Martina and Smith, J Gustav and Brody, Jennifer A and Niemeijer, Maartje N and D{\"o}rr, Marcus and Trompet, Stella and Huffman, Jennifer and Gustafsson, Stefan and Schurmann, Claudia and Kleber, Marcus E and Lyytik{\"a}inen, Leo-Pekka and Sepp{\"a}l{\"a}, Ilkka and Malik, Rainer and Horimoto, Andrea R V R and Perez, Marco and Sinisalo, Juha and Aeschbacher, Stefanie and Th{\'e}riault, S{\'e}bastien and Yao, Jie and Radmanesh, Farid and Weiss, Stefan and Teumer, Alexander and Choi, Seung Hoan and Weng, Lu-Chen and Clauss, Sebastian and Deo, Rajat and Rader, Daniel J and Shah, Svati H and Sun, Albert and Hopewell, Jemma C and Debette, Stephanie and Chauhan, Ganesh and Yang, Qiong and Worrall, Bradford B and Par{\'e}, Guillaume and Kamatani, Yoichiro and Hagemeijer, Yanick P and Verweij, Niek and Siland, Joylene E and Kubo, Michiaki and Smith, Jonathan D and Van Wagoner, David R and Bis, Joshua C and Perz, Siegfried and Psaty, Bruce M and Ridker, Paul M and Magnani, Jared W and Harris, Tamara B and Launer, Lenore J and Shoemaker, M Benjamin and Padmanabhan, Sandosh and Haessler, Jeffrey and Bartz, Traci M and Waldenberger, Melanie and Lichtner, Peter and Arendt, Marina and Krieger, Jose E and K{\"a}h{\"o}nen, Mika and Risch, Lorenz and Mansur, Alfredo J and Peters, Annette and Smith, Blair H and Lind, Lars and Scott, Stuart A and Lu, Yingchang and Bottinger, Erwin B and Hernesniemi, Jussi and Lindgren, Cecilia M and Wong, Jorge A and Huang, Jie and Eskola, Markku and Morris, Andrew P and Ford, Ian and Reiner, Alex P and Delgado, Graciela and Chen, Lin Y and Chen, Yii-Der Ida and Sandhu, Roopinder K and Li, Man and Boerwinkle, Eric and Eisele, Lewin and Lannfelt, Lars and Rost, Natalia and Anderson, Christopher D and Taylor, Kent D and Campbell, Archie and Magnusson, Patrik K and Porteous, David and Hocking, Lynne J and Vlachopoulou, Efthymia and Pedersen, Nancy L and Nikus, Kjell and Orho-Melander, Marju and Hamsten, Anders and Heeringa, Jan and Denny, Joshua C and Kriebel, Jennifer and Darbar, Dawood and Newton-Cheh, Christopher and Shaffer, Christian and Macfarlane, Peter W and Heilmann-Heimbach, Stefanie and Almgren, Peter and Huang, Paul L and Sotoodehnia, Nona and Soliman, Elsayed Z and Uitterlinden, Andr{\'e} G and Hofman, Albert and Franco, Oscar H and V{\"o}lker, Uwe and J{\"o}ckel, Karl-Heinz and Sinner, Moritz F and Lin, Henry J and Guo, Xiuqing and Dichgans, Martin and Ingelsson, Erik and Kooperberg, Charles and Melander, Olle and Loos, Ruth J F and Laurikka, Jari and Conen, David and Rosand, Jonathan and van der Harst, Pim and Lokki, Marja-Liisa and Kathiresan, Sekar and Pereira, Alexandre and Jukema, J Wouter and Hayward, Caroline and Rotter, Jerome I and M{\"a}rz, Winfried and Lehtim{\"a}ki, Terho and Stricker, Bruno H and Chung, Mina K and Felix, Stephan B and Gudnason, Vilmundur and Alonso, Alvaro and Roden, Dan M and K{\"a}{\"a}b, Stefan and Chasman, Daniel I and Heckbert, Susan R and Benjamin, Emelia J and Tanaka, Toshihiro and Lunetta, Kathryn L and Lubitz, Steven A and Ellinor, Patrick T} } @article {7920, title = {Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.}, journal = {Am J Hum Genet}, volume = {103}, year = {2018}, month = {2018 Nov 01}, pages = {691-706}, abstract = {

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5~{\texttimes} 10). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0\% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2018.09.009}, author = {Ligthart, Symen and Vaez, Ahmad and V{\~o}sa, Urmo and Stathopoulou, Maria G and de Vries, Paul S and Prins, Bram P and van der Most, Peter J and Tanaka, Toshiko and Naderi, Elnaz and Rose, Lynda M and Wu, Ying and Karlsson, Robert and Barbalic, Maja and Lin, Honghuang and Pool, Rene and Zhu, Gu and Mace, Aurelien and Sidore, Carlo and Trompet, Stella and Mangino, Massimo and Sabater-Lleal, Maria and Kemp, John P and Abbasi, Ali and Kacprowski, Tim and Verweij, Niek and Smith, Albert V and Huang, Tao and Marzi, Carola and Feitosa, Mary F and Lohman, Kurt K and Kleber, Marcus E and Milaneschi, Yuri and Mueller, Christian and Huq, Mahmudul and Vlachopoulou, Efthymia and Lyytik{\"a}inen, Leo-Pekka and Oldmeadow, Christopher and Deelen, Joris and Perola, Markus and Zhao, Jing Hua and Feenstra, Bjarke and Amini, Marzyeh and Lahti, Jari and Schraut, Katharina E and Fornage, Myriam and Suktitipat, Bhoom and Chen, Wei-Min and Li, Xiaohui and Nutile, Teresa and Malerba, Giovanni and Luan, Jian{\textquoteright}an and Bak, Tom and Schork, Nicholas and del Greco M, Fabiola and Thiering, Elisabeth and Mahajan, Anubha and Marioni, Riccardo E and Mihailov, Evelin and Eriksson, Joel and Ozel, Ayse Bilge and Zhang, Weihua and Nethander, Maria and Cheng, Yu-Ching and Aslibekyan, Stella and Ang, Wei and Gandin, Ilaria and Yengo, Loic and Portas, Laura and Kooperberg, Charles and Hofer, Edith and Rajan, Kumar B and Schurmann, Claudia and den Hollander, Wouter and Ahluwalia, Tarunveer S and Zhao, Jing and Draisma, Harmen H M and Ford, Ian and Timpson, Nicholas and Teumer, Alexander and Huang, Hongyan and Wahl, Simone and Liu, Yongmei and Huang, Jie and Uh, Hae-Won and Geller, Frank and Joshi, Peter K and Yanek, Lisa R and Trabetti, Elisabetta and Lehne, Benjamin and Vozzi, Diego and Verbanck, Marie and Biino, Ginevra and Saba, Yasaman and Meulenbelt, Ingrid and O{\textquoteright}Connell, Jeff R and Laakso, Markku and Giulianini, Franco and Magnusson, Patrik K E and Ballantyne, Christie M and Hottenga, Jouke Jan and Montgomery, Grant W and Rivadineira, Fernando and Rueedi, Rico and Steri, Maristella and Herzig, Karl-Heinz and Stott, David J and Menni, Cristina and Fr{\r a}nberg, Mattias and St Pourcain, Beate and Felix, Stephan B and Pers, Tune H and Bakker, Stephan J L and Kraft, Peter and Peters, Annette and Vaidya, Dhananjay and Delgado, Graciela and Smit, Johannes H and Gro{\ss}mann, Vera and Sinisalo, Juha and Sepp{\"a}l{\"a}, Ilkka and Williams, Stephen R and Holliday, Elizabeth G and Moed, Matthijs and Langenberg, Claudia and R{\"a}ikk{\"o}nen, Katri and Ding, Jingzhong and Campbell, Harry and Sale, Mich{\`e}le M and Chen, Yii-der I and James, Alan L and Ruggiero, Daniela and Soranzo, Nicole and Hartman, Catharina A and Smith, Erin N and Berenson, Gerald S and Fuchsberger, Christian and Hernandez, Dena and Tiesler, Carla M T and Giedraitis, Vilmantas and Liewald, David and Fischer, Krista and Mellstr{\"o}m, Dan and Larsson, Anders and Wang, Yunmei and Scott, William R and Lorentzon, Matthias and Beilby, John and Ryan, Kathleen A and Pennell, Craig E and Vuckovic, Dragana and Balkau, Beverly and Concas, Maria Pina and Schmidt, Reinhold and Mendes de Leon, Carlos F and Bottinger, Erwin P and Kloppenburg, Margreet and Paternoster, Lavinia and Boehnke, Michael and Musk, A W and Willemsen, Gonneke and Evans, David M and Madden, Pamela A F and K{\"a}h{\"o}nen, Mika and Kutalik, Zolt{\'a}n and Zoledziewska, Magdalena and Karhunen, Ville and Kritchevsky, Stephen B and Sattar, Naveed and Lachance, Genevieve and Clarke, Robert and Harris, Tamara B and Raitakari, Olli T and Attia, John R and van Heemst, Diana and Kajantie, Eero and Sorice, Rossella and Gambaro, Giovanni and Scott, Robert A and Hicks, Andrew A and Ferrucci, Luigi and Standl, Marie and Lindgren, Cecilia M and Starr, John M and Karlsson, Magnus and Lind, Lars and Li, Jun Z and Chambers, John C and Mori, Trevor A and de Geus, Eco J C N and Heath, Andrew C and Martin, Nicholas G and Auvinen, Juha and Buckley, Brendan M and de Craen, Anton J M and Waldenberger, Melanie and Strauch, Konstantin and Meitinger, Thomas and Scott, Rodney J and McEvoy, Mark and Beekman, Marian and Bombieri, Cristina and Ridker, Paul M and Mohlke, Karen L and Pedersen, Nancy L and Morrison, Alanna C and Boomsma, Dorret I and Whitfield, John B and Strachan, David P and Hofman, Albert and Vollenweider, Peter and Cucca, Francesco and Jarvelin, Marjo-Riitta and Jukema, J Wouter and Spector, Tim D and Hamsten, Anders and Zeller, Tanja and Uitterlinden, Andr{\'e} G and Nauck, Matthias and Gudnason, Vilmundur and Qi, Lu and Grallert, Harald and Borecki, Ingrid B and Rotter, Jerome I and M{\"a}rz, Winfried and Wild, Philipp S and Lokki, Marja-Liisa and Boyle, Michael and Salomaa, Veikko and Melbye, Mads and Eriksson, Johan G and Wilson, James F and Penninx, Brenda W J H and Becker, Diane M and Worrall, Bradford B and Gibson, Greg and Krauss, Ronald M and Ciullo, Marina and Zaza, Gianluigi and Wareham, Nicholas J and Oldehinkel, Albertine J and Palmer, Lyle J and Murray, Sarah S and Pramstaller, Peter P and Bandinelli, Stefania and Heinrich, Joachim and Ingelsson, Erik and Deary, Ian J and M{\"a}gi, Reedik and Vandenput, Liesbeth and van der Harst, Pim and Desch, Karl C and Kooner, Jaspal S and Ohlsson, Claes and Hayward, Caroline and Lehtim{\"a}ki, Terho and Shuldiner, Alan R and Arnett, Donna K and Beilin, Lawrence J and Robino, Antonietta and Froguel, Philippe and Pirastu, Mario and Jess, Tine and Koenig, Wolfgang and Loos, Ruth J F and Evans, Denis A and Schmidt, Helena and Smith, George Davey and Slagboom, P Eline and Eiriksdottir, Gudny and Morris, Andrew P and Psaty, Bruce M and Tracy, Russell P and Nolte, Ilja M and Boerwinkle, Eric and Visvikis-Siest, Sophie and Reiner, Alex P and Gross, Myron and Bis, Joshua C and Franke, Lude and Franco, Oscar H and Benjamin, Emelia J and Chasman, Daniel I and Dupuis, Jos{\'e}e and Snieder, Harold and Dehghan, Abbas and Alizadeh, Behrooz Z} } @article {7811, title = {Multi-ethnic genome-wide association study for atrial fibrillation.}, journal = {Nat Genet}, volume = {50}, year = {2018}, month = {2018 Sep}, pages = {1225-1233}, abstract = {

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

}, issn = {1546-1718}, doi = {10.1038/s41588-018-0133-9}, author = {Roselli, Carolina and Chaffin, Mark D and Weng, Lu-Chen and Aeschbacher, Stefanie and Ahlberg, Gustav and Albert, Christine M and Almgren, Peter and Alonso, Alvaro and Anderson, Christopher D and Aragam, Krishna G and Arking, Dan E and Barnard, John and Bartz, Traci M and Benjamin, Emelia J and Bihlmeyer, Nathan A and Bis, Joshua C and Bloom, Heather L and Boerwinkle, Eric and Bottinger, Erwin B and Brody, Jennifer A and Calkins, Hugh and Campbell, Archie and Cappola, Thomas P and Carlquist, John and Chasman, Daniel I and Chen, Lin Y and Chen, Yii-Der Ida and Choi, Eue-Keun and Choi, Seung Hoan and Christophersen, Ingrid E and Chung, Mina K and Cole, John W and Conen, David and Cook, James and Crijns, Harry J and Cutler, Michael J and Damrauer, Scott M and Daniels, Brian R and Darbar, Dawood and Delgado, Graciela and Denny, Joshua C and Dichgans, Martin and D{\"o}rr, Marcus and Dudink, Elton A and Dudley, Samuel C and Esa, Nada and Esko, T{\~o}nu and Eskola, Markku and Fatkin, Diane and Felix, Stephan B and Ford, Ian and Franco, Oscar H and Geelhoed, Bastiaan and Grewal, Raji P and Gudnason, Vilmundur and Guo, Xiuqing and Gupta, Namrata and Gustafsson, Stefan and Gutmann, Rebecca and Hamsten, Anders and Harris, Tamara B and Hayward, Caroline and Heckbert, Susan R and Hernesniemi, Jussi and Hocking, Lynne J and Hofman, Albert and Horimoto, Andrea R V R and Huang, Jie and Huang, Paul L and Huffman, Jennifer and Ingelsson, Erik and Ipek, Esra Gucuk and Ito, Kaoru and Jimenez-Conde, Jordi and Johnson, Renee and Jukema, J Wouter and K{\"a}{\"a}b, Stefan and K{\"a}h{\"o}nen, Mika and Kamatani, Yoichiro and Kane, John P and Kastrati, Adnan and Kathiresan, Sekar and Katschnig-Winter, Petra and Kavousi, Maryam and Kessler, Thorsten and Kietselaer, Bas L and Kirchhof, Paulus and Kleber, Marcus E and Knight, Stacey and Krieger, Jose E and Kubo, Michiaki and Launer, Lenore J and Laurikka, Jari and Lehtim{\"a}ki, Terho and Leineweber, Kirsten and Lemaitre, Rozenn N and Li, Man and Lim, Hong Euy and Lin, Henry J and Lin, Honghuang and Lind, Lars and Lindgren, Cecilia M and Lokki, Marja-Liisa and London, Barry and Loos, Ruth J F and Low, Siew-Kee and Lu, Yingchang and Lyytik{\"a}inen, Leo-Pekka and Macfarlane, Peter W and Magnusson, Patrik K and Mahajan, Anubha and Malik, Rainer and Mansur, Alfredo J and Marcus, Gregory M and Margolin, Lauren and Margulies, Kenneth B and M{\"a}rz, Winfried and McManus, David D and Melander, Olle and Mohanty, Sanghamitra and Montgomery, Jay A and Morley, Michael P and Morris, Andrew P and M{\"u}ller-Nurasyid, Martina and Natale, Andrea and Nazarian, Saman and Neumann, Benjamin and Newton-Cheh, Christopher and Niemeijer, Maartje N and Nikus, Kjell and Nilsson, Peter and Noordam, Raymond and Oellers, Heidi and Olesen, Morten S and Orho-Melander, Marju and Padmanabhan, Sandosh and Pak, Hui-Nam and Par{\'e}, Guillaume and Pedersen, Nancy L and Pera, Joanna and Pereira, Alexandre and Porteous, David and Psaty, Bruce M and Pulit, Sara L and Pullinger, Clive R and Rader, Daniel J and Refsgaard, Lena and Ribas{\'e}s, Marta and Ridker, Paul M and Rienstra, Michiel and Risch, Lorenz and Roden, Dan M and Rosand, Jonathan and Rosenberg, Michael A and Rost, Natalia and Rotter, Jerome I and Saba, Samir and Sandhu, Roopinder K and Schnabel, Renate B and Schramm, Katharina and Schunkert, Heribert and Schurman, Claudia and Scott, Stuart A and Sepp{\"a}l{\"a}, Ilkka and Shaffer, Christian and Shah, Svati and Shalaby, Alaa A and Shim, Jaemin and Shoemaker, M Benjamin and Siland, Joylene E and Sinisalo, Juha and Sinner, Moritz F and Slowik, Agnieszka and Smith, Albert V and Smith, Blair H and Smith, J Gustav and Smith, Jonathan D and Smith, Nicholas L and Soliman, Elsayed Z and Sotoodehnia, Nona and Stricker, Bruno H and Sun, Albert and Sun, Han and Svendsen, Jesper H and Tanaka, Toshihiro and Tanriverdi, Kahraman and Taylor, Kent D and Teder-Laving, Maris and Teumer, Alexander and Th{\'e}riault, S{\'e}bastien and Trompet, Stella and Tucker, Nathan R and Tveit, Arnljot and Uitterlinden, Andr{\'e} G and van der Harst, Pim and Van Gelder, Isabelle C and Van Wagoner, David R and Verweij, Niek and Vlachopoulou, Efthymia and V{\"o}lker, Uwe and Wang, Biqi and Weeke, Peter E and Weijs, Bob and Weiss, Raul and Weiss, Stefan and Wells, Quinn S and Wiggins, Kerri L and Wong, Jorge A and Woo, Daniel and Worrall, Bradford B and Yang, Pil-Sung and Yao, Jie and Yoneda, Zachary T and Zeller, Tanja and Zeng, Lingyao and Lubitz, Steven A and Lunetta, Kathryn L and Ellinor, Patrick T} } @article {7576, title = {Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway: a meta-analysis.}, journal = {Diabetologia}, volume = {61}, year = {2018}, month = {2018 Feb}, pages = {317-330}, abstract = {

AIMS/HYPOTHESIS: Sugar-sweetened beverages (SSBs) are a major dietary contributor to fructose intake. A molecular pathway involving the carbohydrate responsive element-binding protein (ChREBP) and the metabolic hormone fibroblast growth factor 21 (FGF21) may influence sugar metabolism and, thereby, contribute to fructose-induced metabolic disease. We hypothesise that common variants in 11 genes involved in fructose metabolism and the ChREBP-FGF21 pathway may interact with SSB intake to exacerbate positive associations between higher SSB intake and glycaemic traits.

METHODS: Data from 11 cohorts (six discovery and five replication) in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided association and interaction results from 34,748 adults of European descent. SSB intake (soft drinks, fruit punches, lemonades or other fruit drinks) was derived from food-frequency questionnaires and food diaries. In fixed-effects meta-analyses, we quantified: (1) the associations between SSBs and glycaemic traits (fasting glucose and fasting insulin); and (2) the interactions between SSBs and 18 independent SNPs related to the ChREBP-FGF21 pathway.

RESULTS: In our combined meta-analyses of discovery and replication cohorts, after adjustment for age, sex, energy intake, BMI and other dietary covariates, each additional serving of SSB intake was associated with higher fasting glucose (β~{\textpm}~SE 0.014~{\textpm}~0.004 [mmol/l], p~=~1.5~{\texttimes}~10-3) and higher fasting insulin (0.030~{\textpm}~0.005 [log e pmol/l], p~=~2.0~{\texttimes}~10-10). No significant interactions on glycaemic traits were observed between SSB intake and selected SNPs. While a suggestive interaction was observed in the discovery cohorts with a SNP (rs1542423) in the β-Klotho (KLB) locus on fasting insulin (0.030~{\textpm}~0.011 log e pmol/l, uncorrected p~=~0.006), results in the replication cohorts and combined meta-analyses were non-significant.

CONCLUSIONS/INTERPRETATION: In this large meta-analysis, we observed that SSB intake was associated with higher fasting glucose and insulin. Although a suggestive interaction with a genetic variant in the ChREBP-FGF21 pathway was observed in the discovery cohorts, this observation was not confirmed in the replication analysis.

TRIAL REGISTRATION: Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT00005487 (Multi-Ethnic Study of Atherosclerosis) and NCT00005152 (Nurses{\textquoteright} Health Study).

}, issn = {1432-0428}, doi = {10.1007/s00125-017-4475-0}, author = {McKeown, Nicola M and Dashti, Hassan S and Ma, Jiantao and Haslam, Danielle E and Kiefte-de Jong, Jessica C and Smith, Caren E and Tanaka, Toshiko and Graff, Mariaelisa and Lemaitre, Rozenn N and Rybin, Denis and Sonestedt, Emily and Frazier-Wood, Alexis C and Mook-Kanamori, Dennis O and Li, Yanping and Wang, Carol A and Leermakers, Elisabeth T M and Mikkil{\"a}, Vera and Young, Kristin L and Mukamal, Kenneth J and Cupples, L Adrienne and Schulz, Christina-Alexandra and Chen, Tzu-An and Li-Gao, Ruifang and Huang, Tao and Oddy, Wendy H and Raitakari, Olli and Rice, Kenneth and Meigs, James B and Ericson, Ulrika and Steffen, Lyn M and Rosendaal, Frits R and Hofman, Albert and K{\"a}h{\"o}nen, Mika and Psaty, Bruce M and Brunkwall, Louise and Uitterlinden, Andr{\'e} G and Viikari, Jorma and Siscovick, David S and Sepp{\"a}l{\"a}, Ilkka and North, Kari E and Mozaffarian, Dariush and Dupuis, Jos{\'e}e and Orho-Melander, Marju and Rich, Stephen S and de Mutsert, Ren{\'e}e and Qi, Lu and Pennell, Craig E and Franco, Oscar H and Lehtim{\"a}ki, Terho and Herman, Mark A} }