@article {8014, title = {Common variants associated with plasma triglycerides and risk for coronary artery disease.}, journal = {Nat Genet}, volume = {45}, year = {2013}, month = {2013 Nov}, pages = {1345-52}, abstract = {

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 {\texttimes} 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism{\textquoteright}s effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

}, keywords = {Biological Transport, Cholesterol, HDL, Cholesterol, LDL, Coronary Artery Disease, Humans, Polymorphism, Single Nucleotide, Risk Factors, Triglycerides}, issn = {1546-1718}, doi = {10.1038/ng.2795}, author = {Do, Ron and Willer, Cristen J and Schmidt, Ellen M and Sengupta, Sebanti and Gao, Chi and Peloso, Gina M and Gustafsson, Stefan and Kanoni, Stavroula and Ganna, Andrea and Chen, Jin and Buchkovich, Martin L and Mora, Samia and Beckmann, Jacques S and Bragg-Gresham, Jennifer L and Chang, Hsing-Yi and Demirkan, Ayse and Den Hertog, Heleen M and Donnelly, Louise A and Ehret, Georg B and Esko, T{\~o}nu and Feitosa, Mary F and Ferreira, Teresa and Fischer, Krista and Fontanillas, Pierre and Fraser, Ross M and Freitag, Daniel F and Gurdasani, Deepti and Heikkil{\"a}, Kauko and Hypp{\"o}nen, Elina and Isaacs, Aaron and Jackson, Anne U and Johansson, Asa and Johnson, Toby and Kaakinen, Marika and Kettunen, Johannes and Kleber, Marcus E and Li, Xiaohui and Luan, Jian{\textquoteright}an and Lyytik{\"a}inen, Leo-Pekka and Magnusson, Patrik K E and Mangino, Massimo and Mihailov, Evelin and Montasser, May E and M{\"u}ller-Nurasyid, Martina and Nolte, Ilja M and O{\textquoteright}Connell, Jeffrey R and Palmer, Cameron D and Perola, Markus and Petersen, Ann-Kristin and Sanna, Serena and Saxena, Richa and Service, Susan K and Shah, Sonia and Shungin, Dmitry and Sidore, Carlo and Song, Ci and Strawbridge, Rona J and Surakka, Ida and Tanaka, Toshiko and Teslovich, Tanya M and Thorleifsson, Gudmar and van den Herik, Evita G and Voight, Benjamin F and Volcik, Kelly A and Waite, Lindsay L and Wong, Andrew and Wu, Ying and Zhang, Weihua and Absher, Devin and Asiki, Gershim and Barroso, In{\^e}s and Been, Latonya F and Bolton, Jennifer L and Bonnycastle, Lori L and Brambilla, Paolo and Burnett, Mary S and Cesana, Giancarlo and Dimitriou, Maria and Doney, Alex S F and D{\"o}ring, Angela and Elliott, Paul and Epstein, Stephen E and Eyjolfsson, Gudmundur Ingi and Gigante, Bruna and Goodarzi, Mark O and Grallert, Harald and Gravito, Martha L and Groves, Christopher J and Hallmans, G{\"o}ran and Hartikainen, Anna-Liisa and Hayward, Caroline and Hernandez, Dena and Hicks, Andrew A and Holm, Hilma and Hung, Yi-Jen and Illig, Thomas and Jones, Michelle R and Kaleebu, Pontiano and Kastelein, John J P and Khaw, Kay-Tee and Kim, Eric and Klopp, Norman and Komulainen, Pirjo and Kumari, Meena and Langenberg, Claudia and Lehtim{\"a}ki, Terho and Lin, Shih-Yi and Lindstr{\"o}m, Jaana and Loos, Ruth J F and Mach, Fran{\c c}ois and McArdle, Wendy L and Meisinger, Christa and Mitchell, Braxton D and M{\"u}ller, Gabrielle and Nagaraja, Ramaiah and Narisu, Narisu and Nieminen, Tuomo V M and Nsubuga, Rebecca N and Olafsson, Isleifur and Ong, Ken K and Palotie, Aarno and Papamarkou, Theodore and Pomilla, Cristina and Pouta, Anneli and Rader, Daniel J and Reilly, Muredach P and Ridker, Paul M and Rivadeneira, Fernando and Rudan, Igor and Ruokonen, Aimo and Samani, Nilesh and Scharnagl, Hubert and Seeley, Janet and Silander, Kaisa and Stan{\v c}{\'a}kov{\'a}, Alena and Stirrups, Kathleen and Swift, Amy J and Tiret, Laurence and Uitterlinden, Andr{\'e} G and van Pelt, L Joost and Vedantam, Sailaja and Wainwright, Nicholas and Wijmenga, Cisca and Wild, Sarah H and Willemsen, Gonneke and Wilsgaard, Tom and Wilson, James F and Young, Elizabeth H and Zhao, Jing Hua and Adair, Linda S and Arveiler, Dominique and Assimes, Themistocles L and Bandinelli, Stefania and Bennett, Franklyn and Bochud, Murielle and Boehm, Bernhard O and Boomsma, Dorret I and Borecki, Ingrid B and Bornstein, Stefan R and Bovet, Pascal and Burnier, Michel and Campbell, Harry and Chakravarti, Aravinda and Chambers, John C and Chen, Yii-Der Ida and Collins, Francis S and Cooper, Richard S and Danesh, John and Dedoussis, George and de Faire, Ulf and Feranil, Alan B and Ferrieres, Jean and Ferrucci, Luigi and Freimer, Nelson B and Gieger, Christian and Groop, Leif C and Gudnason, Vilmundur and Gyllensten, Ulf and Hamsten, Anders and Harris, Tamara B and Hingorani, Aroon and Hirschhorn, Joel N and Hofman, Albert and Hovingh, G Kees and Hsiung, Chao Agnes and Humphries, Steve E and Hunt, Steven C and Hveem, Kristian and Iribarren, Carlos and Jarvelin, Marjo-Riitta and Jula, Antti and K{\"a}h{\"o}nen, Mika and Kaprio, Jaakko and Kes{\"a}niemi, Antero and Kivimaki, Mika and Kooner, Jaspal S and Koudstaal, Peter J and Krauss, Ronald M and Kuh, Diana and Kuusisto, Johanna and Kyvik, Kirsten O and Laakso, Markku and Lakka, Timo A and Lind, Lars and Lindgren, Cecilia M and Martin, Nicholas G and M{\"a}rz, Winfried and McCarthy, Mark I and McKenzie, Colin A and Meneton, Pierre and Metspalu, Andres and Moilanen, Leena and Morris, Andrew D and Munroe, Patricia B and Nj{\o}lstad, Inger and Pedersen, Nancy L and Power, Chris and Pramstaller, Peter P and Price, Jackie F and Psaty, Bruce M and Quertermous, Thomas and Rauramaa, Rainer and Saleheen, Danish and Salomaa, Veikko and Sanghera, Dharambir K and Saramies, Jouko and Schwarz, Peter E H and Sheu, Wayne H-H and Shuldiner, Alan R and Siegbahn, Agneta and Spector, Tim D and Stefansson, Kari and Strachan, David P and Tayo, Bamidele O and Tremoli, Elena and Tuomilehto, Jaakko and Uusitupa, Matti and van Duijn, Cornelia M and Vollenweider, Peter and Wallentin, Lars and Wareham, Nicholas J and Whitfield, John B and Wolffenbuttel, Bruce H R and Altshuler, David and Ordovas, Jose M and Boerwinkle, Eric and Palmer, Colin N A and Thorsteinsdottir, Unnur and Chasman, Daniel I and Rotter, Jerome I and Franks, Paul W and Ripatti, Samuli and Cupples, L Adrienne and Sandhu, Manjinder S and Rich, Stephen S and Boehnke, Michael and Deloukas, Panos and Mohlke, Karen L and Ingelsson, Erik and Abecasis, Goncalo R and Daly, Mark J and Neale, Benjamin M and Kathiresan, Sekar} } @article {6154, title = {Discovery and refinement of loci associated with lipid levels.}, journal = {Nat Genet}, volume = {45}, year = {2013}, month = {2013 Nov}, pages = {1274-1283}, abstract = {

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 {\texttimes} 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

}, keywords = {African Continental Ancestry Group, Asian Continental Ancestry Group, Cholesterol, HDL, Cholesterol, LDL, Coronary Artery Disease, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Lipids, Triglycerides}, issn = {1546-1718}, doi = {10.1038/ng.2797}, author = {Willer, Cristen J and Schmidt, Ellen M and Sengupta, Sebanti and Peloso, Gina M and Gustafsson, Stefan and Kanoni, Stavroula and Ganna, Andrea and Chen, Jin and Buchkovich, Martin L and Mora, Samia and Beckmann, Jacques S and Bragg-Gresham, Jennifer L and Chang, Hsing-Yi and Demirkan, Ayse and Den Hertog, Heleen M and Do, Ron and Donnelly, Louise A and Ehret, Georg B and Esko, T{\~o}nu and Feitosa, Mary F and Ferreira, Teresa and Fischer, Krista and Fontanillas, Pierre and Fraser, Ross M and Freitag, Daniel F and Gurdasani, Deepti and Heikkil{\"a}, Kauko and Hypp{\"o}nen, Elina and Isaacs, Aaron and Jackson, Anne U and Johansson, Asa and Johnson, Toby and Kaakinen, Marika and Kettunen, Johannes and Kleber, Marcus E and Li, Xiaohui and Luan, Jian{\textquoteright}an and Lyytik{\"a}inen, Leo-Pekka and Magnusson, Patrik K E and Mangino, Massimo and Mihailov, Evelin and Montasser, May E and M{\"u}ller-Nurasyid, Martina and Nolte, Ilja M and O{\textquoteright}Connell, Jeffrey R and Palmer, Cameron D and Perola, Markus and Petersen, Ann-Kristin and Sanna, Serena and Saxena, Richa and Service, Susan K and Shah, Sonia and Shungin, Dmitry and Sidore, Carlo and Song, Ci and Strawbridge, Rona J and Surakka, Ida and Tanaka, Toshiko and Teslovich, Tanya M and Thorleifsson, Gudmar and van den Herik, Evita G and Voight, Benjamin F and Volcik, Kelly A and Waite, Lindsay L and Wong, Andrew and Wu, Ying and Zhang, Weihua and Absher, Devin and Asiki, Gershim and Barroso, In{\^e}s and Been, Latonya F and Bolton, Jennifer L and Bonnycastle, Lori L and Brambilla, Paolo and Burnett, Mary S and Cesana, Giancarlo and Dimitriou, Maria and Doney, Alex S F and D{\"o}ring, Angela and Elliott, Paul and Epstein, Stephen E and Ingi Eyjolfsson, Gudmundur and Gigante, Bruna and Goodarzi, Mark O and Grallert, Harald and Gravito, Martha L and Groves, Christopher J and Hallmans, G{\"o}ran and Hartikainen, Anna-Liisa and Hayward, Caroline and Hernandez, Dena and Hicks, Andrew A and Holm, Hilma and Hung, Yi-Jen and Illig, Thomas and Jones, Michelle R and Kaleebu, Pontiano and Kastelein, John J P and Khaw, Kay-Tee and Kim, Eric and Klopp, Norman and Komulainen, Pirjo and Kumari, Meena and Langenberg, Claudia and Lehtim{\"a}ki, Terho and Lin, Shih-Yi and Lindstr{\"o}m, Jaana and Loos, Ruth J F and Mach, Fran{\c c}ois and McArdle, Wendy L and Meisinger, Christa and Mitchell, Braxton D and M{\"u}ller, Gabrielle and Nagaraja, Ramaiah and Narisu, Narisu and Nieminen, Tuomo V M and Nsubuga, Rebecca N and Olafsson, Isleifur and Ong, Ken K and Palotie, Aarno and Papamarkou, Theodore and Pomilla, Cristina and Pouta, Anneli and Rader, Daniel J and Reilly, Muredach P and Ridker, Paul M and Rivadeneira, Fernando and Rudan, Igor and Ruokonen, Aimo and Samani, Nilesh and Scharnagl, Hubert and Seeley, Janet and Silander, Kaisa and Stan{\v c}{\'a}kov{\'a}, Alena and Stirrups, Kathleen and Swift, Amy J and Tiret, Laurence and Uitterlinden, Andr{\'e} G and van Pelt, L Joost and Vedantam, Sailaja and Wainwright, Nicholas and Wijmenga, Cisca and Wild, Sarah H and Willemsen, Gonneke and Wilsgaard, Tom and Wilson, James F and Young, Elizabeth H and Zhao, Jing Hua and Adair, Linda S and Arveiler, Dominique and Assimes, Themistocles L and Bandinelli, Stefania and Bennett, Franklyn and Bochud, Murielle and Boehm, Bernhard O and Boomsma, Dorret I and Borecki, Ingrid B and Bornstein, Stefan R and Bovet, Pascal and Burnier, Michel and Campbell, Harry and Chakravarti, Aravinda and Chambers, John C and Chen, Yii-Der Ida and Collins, Francis S and Cooper, Richard S and Danesh, John and Dedoussis, George and de Faire, Ulf and Feranil, Alan B and Ferrieres, Jean and Ferrucci, Luigi and Freimer, Nelson B and Gieger, Christian and Groop, Leif C and Gudnason, Vilmundur and Gyllensten, Ulf and Hamsten, Anders and Harris, Tamara B and Hingorani, Aroon and Hirschhorn, Joel N and Hofman, Albert and Hovingh, G Kees and Hsiung, Chao Agnes and Humphries, Steve E and Hunt, Steven C and Hveem, Kristian and Iribarren, Carlos and Jarvelin, Marjo-Riitta and Jula, Antti and K{\"a}h{\"o}nen, Mika and Kaprio, Jaakko and Kes{\"a}niemi, Antero and Kivimaki, Mika and Kooner, Jaspal S and Koudstaal, Peter J and Krauss, Ronald M and Kuh, Diana and Kuusisto, Johanna and Kyvik, Kirsten O and Laakso, Markku and Lakka, Timo A and Lind, Lars and Lindgren, Cecilia M and Martin, Nicholas G and M{\"a}rz, Winfried and McCarthy, Mark I and McKenzie, Colin A and Meneton, Pierre and Metspalu, Andres and Moilanen, Leena and Morris, Andrew D and Munroe, Patricia B and Nj{\o}lstad, Inger and Pedersen, Nancy L and Power, Chris and Pramstaller, Peter P and Price, Jackie F and Psaty, Bruce M and Quertermous, Thomas and Rauramaa, Rainer and Saleheen, Danish and Salomaa, Veikko and Sanghera, Dharambir K and Saramies, Jouko and Schwarz, Peter E H and Sheu, Wayne H-H and Shuldiner, Alan R and Siegbahn, Agneta and Spector, Tim D and Stefansson, Kari and Strachan, David P and Tayo, Bamidele O and Tremoli, Elena and Tuomilehto, Jaakko and Uusitupa, Matti and van Duijn, Cornelia M and Vollenweider, Peter and Wallentin, Lars and Wareham, Nicholas J and Whitfield, John B and Wolffenbuttel, Bruce H R and Ordovas, Jose M and Boerwinkle, Eric and Palmer, Colin N A and Thorsteinsdottir, Unnur and Chasman, Daniel I and Rotter, Jerome I and Franks, Paul W and Ripatti, Samuli and Cupples, L Adrienne and Sandhu, Manjinder S and Rich, Stephen S and Boehnke, Michael and Deloukas, Panos and Kathiresan, Sekar and Mohlke, Karen L and Ingelsson, Erik and Abecasis, Goncalo R} } @article {6152, title = {Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.}, journal = {Nat Genet}, volume = {45}, year = {2013}, month = {2013 May}, pages = {501-12}, abstract = {

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

}, keywords = {Anthropometry, Body Height, Body Mass Index, Case-Control Studies, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Obesity, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Waist-Hip Ratio}, issn = {1546-1718}, doi = {10.1038/ng.2606}, author = {Berndt, Sonja I and Gustafsson, Stefan and M{\"a}gi, Reedik and Ganna, Andrea and Wheeler, Eleanor and Feitosa, Mary F and Justice, Anne E and Monda, Keri L and Croteau-Chonka, Damien C and Day, Felix R and Esko, T{\~o}nu and Fall, Tove and Ferreira, Teresa and Gentilini, Davide and Jackson, Anne U and Luan, Jian{\textquoteright}an and Randall, Joshua C and Vedantam, Sailaja and Willer, Cristen J and Winkler, Thomas W and Wood, Andrew R and Workalemahu, Tsegaselassie and Hu, Yi-Juan and Lee, Sang Hong and Liang, Liming and Lin, Dan-Yu and Min, Josine L and Neale, Benjamin M and Thorleifsson, Gudmar and Yang, Jian and Albrecht, Eva and Amin, Najaf and Bragg-Gresham, Jennifer L and Cadby, Gemma and den Heijer, Martin and Eklund, Niina and Fischer, Krista and Goel, Anuj and Hottenga, Jouke-Jan and Huffman, Jennifer E and Jarick, Ivonne and Johansson, Asa and Johnson, Toby and Kanoni, Stavroula and Kleber, Marcus E and K{\"o}nig, Inke R and Kristiansson, Kati and Kutalik, Zolt{\'a}n and Lamina, Claudia and Lecoeur, C{\'e}cile and Li, Guo and Mangino, Massimo and McArdle, Wendy L and Medina-G{\'o}mez, Carolina and M{\"u}ller-Nurasyid, Martina and Ngwa, Julius S and Nolte, Ilja M and Paternoster, Lavinia and Pechlivanis, Sonali and Perola, Markus and Peters, Marjolein J and Preuss, Michael and Rose, Lynda M and Shi, Jianxin and Shungin, Dmitry and Smith, Albert Vernon and Strawbridge, Rona J and Surakka, Ida and Teumer, Alexander and Trip, Mieke D and Tyrer, Jonathan and van Vliet-Ostaptchouk, Jana V and Vandenput, Liesbeth and Waite, Lindsay L and Zhao, Jing Hua and Absher, Devin and Asselbergs, Folkert W and Atalay, Mustafa and Attwood, Antony P and Balmforth, Anthony J and Basart, Hanneke and Beilby, John and Bonnycastle, Lori L and Brambilla, Paolo and Bruinenberg, Marcel and Campbell, Harry and Chasman, Daniel I and Chines, Peter S and Collins, Francis S and Connell, John M and Cookson, William O and de Faire, Ulf and de Vegt, Femmie and Dei, Mariano and Dimitriou, Maria and Edkins, Sarah and Estrada, Karol and Evans, David M and Farrall, Martin and Ferrario, Marco M and Ferrieres, Jean and Franke, Lude and Frau, Francesca and Gejman, Pablo V and Grallert, Harald and Gr{\"o}nberg, Henrik and Gudnason, Vilmundur and Hall, Alistair S and Hall, Per and Hartikainen, Anna-Liisa and Hayward, Caroline and Heard-Costa, Nancy L and Heath, Andrew C and Hebebrand, Johannes and Homuth, Georg and Hu, Frank B and Hunt, Sarah E and Hypp{\"o}nen, Elina and Iribarren, Carlos and Jacobs, Kevin B and Jansson, John-Olov and Jula, Antti and K{\"a}h{\"o}nen, Mika and Kathiresan, Sekar and Kee, Frank and Khaw, Kay-Tee and Kivimaki, Mika and Koenig, Wolfgang and Kraja, Aldi T and Kumari, Meena and Kuulasmaa, Kari and Kuusisto, Johanna and Laitinen, Jaana H and Lakka, Timo A and Langenberg, Claudia and Launer, Lenore J and Lind, Lars and Lindstr{\"o}m, Jaana and Liu, Jianjun and Liuzzi, Antonio and Lokki, Marja-Liisa and Lorentzon, Mattias and Madden, Pamela A and Magnusson, Patrik K and Manunta, Paolo and Marek, Diana and M{\"a}rz, Winfried and Mateo Leach, Irene and McKnight, Barbara and Medland, Sarah E and Mihailov, Evelin and Milani, Lili and Montgomery, Grant W and Mooser, Vincent and M{\"u}hleisen, Thomas W and Munroe, Patricia B and Musk, Arthur W and Narisu, Narisu and Navis, Gerjan and Nicholson, George and Nohr, Ellen A and Ong, Ken K and Oostra, Ben A and Palmer, Colin N A and Palotie, Aarno and Peden, John F and Pedersen, Nancy and Peters, Annette and Polasek, Ozren and Pouta, Anneli and Pramstaller, Peter P and Prokopenko, Inga and P{\"u}tter, Carolin and Radhakrishnan, Aparna and Raitakari, Olli and Rendon, Augusto and Rivadeneira, Fernando and Rudan, Igor and Saaristo, Timo E and Sambrook, Jennifer G and Sanders, Alan R and Sanna, Serena and Saramies, Jouko and Schipf, Sabine and Schreiber, Stefan and Schunkert, Heribert and Shin, So-Youn and Signorini, Stefano and Sinisalo, Juha and Skrobek, Boris and Soranzo, Nicole and Stan{\v c}{\'a}kov{\'a}, Alena and Stark, Klaus and Stephens, Jonathan C and Stirrups, Kathleen and Stolk, Ronald P and Stumvoll, Michael and Swift, Amy J and Theodoraki, Eirini V and Thorand, Barbara and Tr{\'e}gou{\"e}t, David-Alexandre and Tremoli, Elena and van der Klauw, Melanie M and van Meurs, Joyce B J and Vermeulen, Sita H and Viikari, Jorma and Virtamo, Jarmo and Vitart, Veronique and Waeber, G{\'e}rard and Wang, Zhaoming and Widen, Elisabeth and Wild, Sarah H and Willemsen, Gonneke and Winkelmann, Bernhard R and Witteman, Jacqueline C M and Wolffenbuttel, Bruce H R and Wong, Andrew and Wright, Alan F and Zillikens, M Carola and Amouyel, Philippe and Boehm, Bernhard O and Boerwinkle, Eric and Boomsma, Dorret I and Caulfield, Mark J and Chanock, Stephen J and Cupples, L Adrienne and Cusi, Daniele and Dedoussis, George V and Erdmann, Jeanette and Eriksson, Johan G and Franks, Paul W and Froguel, Philippe and Gieger, Christian and Gyllensten, Ulf and Hamsten, Anders and Harris, Tamara B and Hengstenberg, Christian and Hicks, Andrew A and Hingorani, Aroon and Hinney, Anke and Hofman, Albert and Hovingh, Kees G and Hveem, Kristian and Illig, Thomas and Jarvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Keinanen-Kiukaanniemi, Sirkka M and Kiemeney, Lambertus A and Kuh, Diana and Laakso, Markku and Lehtim{\"a}ki, Terho and Levinson, Douglas F and Martin, Nicholas G and Metspalu, Andres and Morris, Andrew D and Nieminen, Markku S and Nj{\o}lstad, Inger and Ohlsson, Claes and Oldehinkel, Albertine J and Ouwehand, Willem H and Palmer, Lyle J and Penninx, Brenda and Power, Chris and Province, Michael A and Psaty, Bruce M and Qi, Lu and Rauramaa, Rainer and Ridker, Paul M and Ripatti, Samuli and Salomaa, Veikko and Samani, Nilesh J and Snieder, Harold and S{\o}rensen, Thorkild I A and Spector, Timothy D and Stefansson, Kari and T{\"o}njes, Anke and Tuomilehto, Jaakko and Uitterlinden, Andr{\'e} G and Uusitupa, Matti and van der Harst, Pim and Vollenweider, Peter and Wallaschofski, Henri and Wareham, Nicholas J and Watkins, Hugh and Wichmann, H-Erich and Wilson, James F and Abecasis, Goncalo R and Assimes, Themistocles L and Barroso, In{\^e}s and Boehnke, Michael and Borecki, Ingrid B and Deloukas, Panos and Fox, Caroline S and Frayling, Timothy and Groop, Leif C and Haritunian, Talin and Heid, Iris M and Hunter, David and Kaplan, Robert C and Karpe, Fredrik and Moffatt, Miriam F and Mohlke, Karen L and O{\textquoteright}Connell, Jeffrey R and Pawitan, Yudi and Schadt, Eric E and Schlessinger, David and Steinthorsdottir, Valgerdur and Strachan, David P and Thorsteinsdottir, Unnur and van Duijn, Cornelia M and Visscher, Peter M and Di Blasio, Anna Maria and Hirschhorn, Joel N and Lindgren, Cecilia M and Morris, Andrew P and Meyre, David and Scherag, Andre and McCarthy, Mark I and Speliotes, Elizabeth K and North, Kari E and Loos, Ruth J F and Ingelsson, Erik} } @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 {6028, title = {Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.}, journal = {PLoS Genet}, volume = {9}, year = {2013}, month = {2013 Jun}, pages = {e1003500}, abstract = {

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5\%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5{\texttimes}10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

}, keywords = {Anthropometry, Body Height, Body Mass Index, Body Weight, Body Weights and Measures, Female, Genetic Loci, Genome, Human, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Sex Characteristics, Waist Circumference, Waist-Hip Ratio}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003500}, author = {Randall, Joshua C and Winkler, Thomas W and Kutalik, Zolt{\'a}n and Berndt, Sonja I and Jackson, Anne U and Monda, Keri L and Kilpel{\"a}inen, Tuomas O and Esko, T{\~o}nu and M{\"a}gi, Reedik and Li, Shengxu and Workalemahu, Tsegaselassie and Feitosa, Mary F and Croteau-Chonka, Damien C and Day, Felix R and Fall, Tove and Ferreira, Teresa and Gustafsson, Stefan and Locke, Adam E and Mathieson, Iain and Scherag, Andre and Vedantam, Sailaja and Wood, Andrew R and Liang, Liming and Steinthorsdottir, Valgerdur and Thorleifsson, Gudmar and Dermitzakis, Emmanouil T and Dimas, Antigone S and Karpe, Fredrik and Min, Josine L and Nicholson, George and Clegg, Deborah J and Person, Thomas and Krohn, Jon P and Bauer, Sabrina and Buechler, Christa and Eisinger, Kristina and Bonnefond, Am{\'e}lie and Froguel, Philippe and Hottenga, Jouke-Jan and Prokopenko, Inga and Waite, Lindsay L and Harris, Tamara B and Smith, Albert Vernon and Shuldiner, Alan R and McArdle, Wendy L and Caulfield, Mark J and Munroe, Patricia B and Gr{\"o}nberg, Henrik and Chen, Yii-Der Ida and Li, Guo and Beckmann, Jacques S and Johnson, Toby and Thorsteinsdottir, Unnur and Teder-Laving, Maris and Khaw, Kay-Tee and Wareham, Nicholas J and Zhao, Jing Hua and Amin, Najaf and Oostra, Ben A and Kraja, Aldi T and Province, Michael A and Cupples, L Adrienne and Heard-Costa, Nancy L and Kaprio, Jaakko and Ripatti, Samuli and Surakka, Ida and Collins, Francis S and Saramies, Jouko and Tuomilehto, Jaakko and Jula, Antti and Salomaa, Veikko and Erdmann, Jeanette and Hengstenberg, Christian and Loley, Christina and Schunkert, Heribert and Lamina, Claudia and Wichmann, H Erich and Albrecht, Eva and Gieger, Christian and Hicks, Andrew A and Johansson, Asa and Pramstaller, Peter P and Kathiresan, Sekar and Speliotes, Elizabeth K and Penninx, Brenda and Hartikainen, Anna-Liisa and Jarvelin, Marjo-Riitta and Gyllensten, Ulf and Boomsma, Dorret I and Campbell, Harry and Wilson, James F and Chanock, Stephen J and Farrall, Martin and Goel, Anuj and Medina-G{\'o}mez, Carolina and Rivadeneira, Fernando and Estrada, Karol and Uitterlinden, Andr{\'e} G and Hofman, Albert and Zillikens, M Carola and den Heijer, Martin and Kiemeney, Lambertus A and Maschio, Andrea and Hall, Per and Tyrer, Jonathan and Teumer, Alexander and V{\"o}lzke, Henry and Kovacs, Peter and T{\"o}njes, Anke and Mangino, Massimo and Spector, Tim D and Hayward, Caroline and Rudan, Igor and Hall, Alistair S and Samani, Nilesh J and Attwood, Antony Paul and Sambrook, Jennifer G and Hung, Joseph and Palmer, Lyle J and Lokki, Marja-Liisa and Sinisalo, Juha and Boucher, Gabrielle and Huikuri, Heikki and Lorentzon, Mattias and Ohlsson, Claes and Eklund, Niina and Eriksson, Johan G and Barlassina, Cristina and Rivolta, Carlo and Nolte, Ilja M and Snieder, Harold and van der Klauw, Melanie M and van Vliet-Ostaptchouk, Jana V and Gejman, Pablo V and Shi, Jianxin and Jacobs, Kevin B and Wang, Zhaoming and Bakker, Stephan J L and Mateo Leach, Irene and Navis, Gerjan and van der Harst, Pim and Martin, Nicholas G and Medland, Sarah E and Montgomery, Grant W and Yang, Jian and Chasman, Daniel I and Ridker, Paul M and Rose, Lynda M and Lehtim{\"a}ki, Terho and Raitakari, Olli and Absher, Devin and Iribarren, Carlos and Basart, Hanneke and Hovingh, Kees G and Hypp{\"o}nen, Elina and Power, Chris and Anderson, Denise and Beilby, John P and Hui, Jennie and Jolley, Jennifer and Sager, Hendrik and Bornstein, Stefan R and Schwarz, Peter E H and Kristiansson, Kati and Perola, Markus and Lindstr{\"o}m, Jaana and Swift, Amy J and Uusitupa, Matti and Atalay, Mustafa and Lakka, Timo A and Rauramaa, Rainer and Bolton, Jennifer L and Fowkes, Gerry and Fraser, Ross M and Price, Jackie F and Fischer, Krista and Krjut{\r a} Kov, Kaarel and Metspalu, Andres and Mihailov, Evelin and Langenberg, Claudia and Luan, Jian{\textquoteright}an and Ong, Ken K and Chines, Peter S and Keinanen-Kiukaanniemi, Sirkka M and Saaristo, Timo E and Edkins, Sarah and Franks, Paul W and Hallmans, G{\"o}ran and Shungin, Dmitry and Morris, Andrew David and Palmer, Colin N A and Erbel, Raimund and Moebus, Susanne and N{\"o}then, Markus M and Pechlivanis, Sonali and Hveem, Kristian and Narisu, Narisu and Hamsten, Anders and Humphries, Steve E and Strawbridge, Rona J and Tremoli, Elena and Grallert, Harald and Thorand, Barbara and Illig, Thomas and Koenig, Wolfgang and M{\"u}ller-Nurasyid, Martina and Peters, Annette and Boehm, Bernhard O and Kleber, Marcus E and M{\"a}rz, Winfried and Winkelmann, Bernhard R and Kuusisto, Johanna and Laakso, Markku and Arveiler, Dominique and Cesana, Giancarlo and Kuulasmaa, Kari and Virtamo, Jarmo and Yarnell, John W G and Kuh, Diana and Wong, Andrew and Lind, Lars and de Faire, Ulf and Gigante, Bruna and Magnusson, Patrik K E and Pedersen, Nancy L and Dedoussis, George and Dimitriou, Maria and Kolovou, Genovefa and Kanoni, Stavroula and Stirrups, Kathleen and Bonnycastle, Lori L and Nj{\o}lstad, Inger and Wilsgaard, Tom and Ganna, Andrea and Rehnberg, Emil and Hingorani, Aroon and Kivimaki, Mika and Kumari, Meena and Assimes, Themistocles L and Barroso, In{\^e}s and Boehnke, Michael and Borecki, Ingrid B and Deloukas, Panos and Fox, Caroline S and Frayling, Timothy and Groop, Leif C and Haritunians, Talin and Hunter, David and Ingelsson, Erik and Kaplan, Robert and Mohlke, Karen L and O{\textquoteright}Connell, Jeffrey R and Schlessinger, David and Strachan, David P and Stefansson, Kari and van Duijn, Cornelia M and Abecasis, Goncalo R and McCarthy, Mark I and Hirschhorn, Joel N and Qi, Lu and Loos, Ruth J F and Lindgren, Cecilia M and North, Kari E and Heid, Iris M} } @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} }