@article {9526, title = {Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.}, journal = {Nat Genet}, volume = {50}, year = {2018}, month = {2018 Jan}, pages = {26-41}, abstract = {

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5\%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed~to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01\%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI~confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

}, issn = {1546-1718}, doi = {10.1038/s41588-017-0011-x}, author = {Turcot, Val{\'e}rie and Lu, Yingchang and Highland, Heather M and Schurmann, Claudia and Justice, Anne E and Fine, Rebecca S and Bradfield, Jonathan P and T{\~o}nu Esko and Giri, Ayush and Graff, Mariaelisa and Guo, Xiuqing and Hendricks, Audrey E and Karaderi, Tugce and Lempradl, Adelheid and Locke, Adam E and Mahajan, Anubha and Marouli, Eirini and Sivapalaratnam, Suthesh and Young, Kristin L and Alfred, Tamuno and Feitosa, Mary F and Masca, Nicholas G D and Alisa Manning and Medina-Gomez, Carolina and Mudgal, Poorva and Ng, Maggie C Y and Reiner, Alex P and Vedantam, Sailaja and Willems, Sara M and Thomas W Winkler and Gon{\c c}alo R Abecasis and Aben, Katja K and Alam, Dewan S and Alharthi, Sameer E and Matthew A. Allison and Amouyel, Philippe and Asselbergs, Folkert W and Auer, Paul L and Balkau, Beverley and Bang, Lia E and Barroso, In{\^e}s and Bastarache, Lisa and Benn, Marianne and Bergmann, Sven and Bielak, Lawrence F and Bl{\"u}her, Matthias and Boehnke, Michael and Boeing, Heiner and Boerwinkle, Eric and B{\"o}ger, Carsten A and Bork-Jensen, Jette and Bots, Michiel L and Erwin P Bottinger and Bowden, Donald W and Brandslund, Ivan and Breen, Gerome and Brilliant, Murray H and Broer, Linda and Brumat, Marco and Burt, Amber A and Adam S Butterworth and Campbell, Peter T and Cappellani, Stefania and Carey, David J and Catamo, Eulalia and Caulfield, Mark J and Chambers, John C and Daniel I Chasman and Yii-Der I Chen and Chowdhury, Rajiv and Cramer Christensen and Chu, Audrey Y and Cocca, Massimiliano and Collins, Francis S and Cook, James P and Corley, Janie and Jordi Corominas Galbany and Cox, Amanda J and Crosslin, David S and Cuellar-Partida, Gabriel and D{\textquoteright}Eustacchio, Angela and Danesh, John and Gail Davies and Bakker, Paul I W and Groot, Mark C H and Mutsert, Ren{\'e}e and Ian J Deary and George Dedoussis and Ellen W Demerath and Heijer, Martin and Anneke I den Hollander and Hester M den Ruijter and Joe G Dennis and Denny, Josh C and Angelantonio, Emanuele and Drenos, Fotios and Du, Mengmeng and Dub{\'e}, Marie-Pierre and Dunning, Alison M and Easton, Douglas F and Edwards, Todd L and Ellinghaus, David and Ellinor, Patrick T and Elliott, Paul and Evangelou, Evangelos and Farmaki, Aliki-Eleni and Farooqi, I Sadaf and Jessica Faul and Fauser, Sascha and Feng, Shuang and Ferrannini, Ele and Ferri{\`e}res, Jean and Florez, Jose C and Ford, Ian and Myriam Fornage and Franco, Oscar H and Franke, Andre and Franks, Paul W and Friedrich, Nele and Frikke-Schmidt, Ruth and Galesloot, Tessel E and Gan, Wei and Gandin, Ilaria and Paolo P. Gasparini and Gibson, Jane and Giedraitis, Vilmantas and Gjesing, Anette P and Gordon-Larsen, Penny and Gorski, Mathias and Hans-J{\"o}rgen Grabe and Grant, Struan F A and Grarup, Niels and Griffiths, Helen L and Grove, Megan L and Gudnason, Vilmundur and Gustafsson, Stefan and Jeffrey Haessler and Hakonarson, Hakon and Anke R Hammerschlag and Hansen, Torben and Tamara B Harris and Andrew T Hattersley and Have, Christian T and Caroline Hayward and He, Liang and Heard-Costa, Nancy L and Andrew C Heath and Iris M Heid and Helgeland, {\O}yvind and Hernesniemi, Jussi and Hewitt, Alex W and Oddgeir L Holmen and Hovingh, G Kees and Howson, Joanna M M and Hu, Yao and Huang, Paul L and Huffman, Jennifer E and Mohammed Arfan Ikram and Ingelsson, Erik and Jackson, Anne U and Jansson, Jan-H{\r a}kan and Jarvik, Gail P and Jensen, Gorm B and Jia, Yucheng and Johansson, Stefan and J{\o}rgensen, Marit E and J{\o}rgensen, Torben and Jukema, J Wouter and Kahali, Bratati and Kahn, Ren{\'e} S and K{\"a}h{\"o}nen, Mika and Kamstrup, Pia R and Kanoni, Stavroula and Kaprio, Jaakko and Karaleftheri, Maria and Sharon L R Kardia and Karpe, Fredrik and Kathiresan, Sekar and Kee, Frank and Lambertus A Kiemeney and Eric S Kim and Kitajima, Hidetoshi and Komulainen, Pirjo and Kooner, Jaspal S and Charles Kooperberg and Korhonen, Tellervo and Kovacs, Peter and Kuivaniemi, Helena and Kutalik, Zolt{\'a}n and Kuulasmaa, Kari and Kuusisto, Johanna and Laakso, Markku and Lakka, Timo A and Lamparter, David and Lange, Ethan M and Leslie A Lange and Langenberg, Claudia and Eric B Larson and Lee, Nanette R and Lehtim{\"a}ki, Terho and Lewis, Cora E and Li, Huaixing and Li, Jin and Li-Gao, Ruifang and Lin, Honghuang and Lin, Keng-Hung and Lin, Li-An and Lin, Xu and Lars Lind and Lindstr{\"o}m, Jaana and Linneberg, Allan and Liu, Ching-Ti and Liu, Dajiang J and Yongmei Liu and Ken Sin Lo and Lophatananon, Artitaya and Lotery, Andrew J and Loukola, Anu and Luan, Jian{\textquoteright}an and Lubitz, Steven A and Lyytik{\"a}inen, Leo-Pekka and M{\"a}nnist{\"o}, Satu and Marenne, Ga{\"e}lle and Mazul, Angela L and McCarthy, Mark I and McKean-Cowdin, Roberta and Sarah E Medland and Meidtner, Karina and Lili Milani and Mistry, Vanisha and Mitchell, Paul and Mohlke, Karen L and Moilanen, Leena and Moitry, Marie and Grant W Montgomery and Dennis O Mook-Kanamori and Moore, Carmel and Mori, Trevor A and Morris, Andrew D and Morris, Andrew P and M{\"u}ller-Nurasyid, Martina and Munroe, Patricia B and Michael A Nalls and Narisu, Narisu and Nelson, Christopher P and Neville, Matt and Sune Fallgaard Nielsen and Nikus, Kjell and Nj{\o}lstad, P{\r a}l R and B{\o}rge G Nordestgaard and Nyholt, Dale R and Jeff O{\textquoteright}Connell and O{\textquoteright}Donoghue, Michelle L and Ophoff, Roel A and Owen, Katharine R and Packard, Chris J and Padmanabhan, Sandosh and Palmer, Colin N A and Palmer, Nicholette D and Pasterkamp, Gerard and Patel, Aniruddh P and Pattie, Alison and Pedersen, Oluf and Peissig, Peggy L and Peloso, Gina M and Pennell, Craig E and Markus Perola and Perry, James A and Perry, John R B and Pers, Tune H and Person, Thomas N and Peters, Annette and Petersen, Eva R B and Peyser, Patricia A and Pirie, Ailith and Polasek, Ozren and Tinca J Polderman and Puolijoki, Hannu and Olli T Raitakari and Rasheed, Asif and Rauramaa, Rainer and Reilly, Dermot F and Renstrom, Frida and Rheinberger, Myriam and Ridker, Paul M and Rioux, John D and Rivas, Manuel A and Roberts, David J and Neil R Robertson and Robino, Antonietta and Rolandsson, Olov and Rudan, Igor and Ruth, Katherine S and Saleheen, Danish and Veikko Salomaa and Nilesh J Samani and Sapkota, Yadav and Sattar, Naveed and Schoen, Robert E and Schreiner, Pamela J and Schulze, Matthias B and Scott, Robert A and Segura-Lepe, Marcelo P and Svati H Shah and Sheu, Wayne H-H and Sim, Xueling and Slater, Andrew J and Small, Kerrin S and Albert Vernon Smith and Southam, Lorraine and Timothy Spector and Elizabeth K Speliotes and John M Starr and Stefansson, Kari and Steinthorsdottir, Valgerdur and Kathleen E Stirrups and Strauch, Konstantin and Heather M Stringham and Stumvoll, Michael and Sun, Liang and Surendran, Praveen and Swift, Amy J and Tada, Hayato and Tansey, Katherine E and Tardif, Jean-Claude and Kent D Taylor and Teumer, Alexander and Thompson, Deborah J and Thorleifsson, Gudmar and Thorsteinsdottir, Unnur and Thuesen, Betina H and T{\"o}njes, Anke and Tromp, Gerard and Trompet, Stella and Tsafantakis, Emmanouil and Tuomilehto, Jaakko and Tybjaerg-Hansen, Anne and Tyrer, Jonathan P and Uher, Rudolf and Andr{\'e} G Uitterlinden and Uusitupa, Matti and Laan, Sander W and Duijn, Cornelia M and Leeuwen, Nienke and van Setten, Jessica and Vanhala, Mauno and Varbo, Anette and Varga, Tibor V and Varma, Rohit and Digna R Velez Edwards and Vermeulen, Sita H and Veronesi, Giovanni and Vestergaard, Henrik and Vitart, Veronique and Vogt, Thomas F and V{\"o}lker, Uwe and Vuckovic, Dragana and Wagenknecht, Lynne E and Walker, Mark and Wallentin, Lars and Wang, Feijie and Wang, Carol A and Wang, Shuai and Wang, Yiqin and Erin B Ware and Wareham, Nicholas J and Warren, Helen R and Dawn M Waterworth and Wessel, Jennifer and White, Harvey D and Willer, Cristen J and Wilson, James G and Daniel Witte and Andrew R Wood and Wu, Ying and Yaghootkar, Hanieh and Yao, Jie and Yao, Pang and Laura M Yerges-Armstrong and Young, Robin and Zeggini, Eleftheria and Zhan, Xiaowei and Zhang, Weihua and Wei Zhao and Zhou, Wei and Krina T Zondervan and Rotter, Jerome I and Pospisilik, John A and Fernando Rivadeneira and Ingrid B Borecki and Deloukas, Panos and Timothy M Frayling and Lettre, Guillaume and Kari E North and Lindgren, Cecilia M and Joel N Hirschhron and Ruth J F Loos} } @article {12131, title = {Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.}, journal = {Nature Communications}, volume = {8}, year = {2017}, 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.

}, keywords = {Alleles, Body Mass Index, Coronary Disease, Education, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-DQ alpha-Chains, HLA-DRB1 Chains, Humans, Insulin Resistance, Life Style, Lipoprotein(a), Lipoproteins, HDL, Longevity, Lung Neoplasms, Obesity, Polymorphism, Single Nucleotide, Smoking, Socioeconomic factors}, issn = {2041-1723}, doi = {10.1038/s41467-017-00934-5}, author = {Joshi, Peter K and Nicola Pirastu and Kentistou, Katherine A and Fischer, Krista and Edith Hofer and Schraut, Katharina E and Clark, David W and Nutile, Teresa and Barnes, Catriona L K and Paul Rhj Timmers 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-Gomez, Carolina and Traci M Bartz and Trompet, Stella and Leslie A Lange 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 Ellen W Demerath and Demuth, Ilja and Jessica Faul and Ford, Ian and Gialluisi, Alessandro and G{\"o}gele, Martin and Graff, Mariaelisa and Aroon Hingorani and Jouke-Jan Hottenga 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 Sarah E Medland and Lili Milani and Nagy, Reka and William E R Ollier and Peyser, Patricia A and Pramstaller, Peter P and Ridker, Paul M and Fernando Rivadeneira 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 Alan B Zonderman and Lehtim{\"a}ki, Terho and Michele K Evans and Pirastu, Mario and Fuchsberger, Christian and Bertram, Lars and Pendleton, Neil and Sharon L R Kardia and Ciullo, Marina and Becker, Diane M and Wong, Andrew and Psaty, Bruce M and Cornelia M van Duijn and Wilson, James G and Jukema, J Wouter and Lambertus A Kiemeney and Andr{\'e} G Uitterlinden and Franceschini, Nora and Kari E North and David R Weir and Andres Metspalu and Dorret I Boomsma and Caroline Hayward and Daniel I Chasman and Nicholas G Martin and Sattar, Naveed and Campbell, Harry and T{\~o}nu Esko and Kutalik, Zolt{\'a}n and James F Wilson} } @article {8886, title = {Rare and low-frequency coding variants alter human adult height.}, journal = {Nature}, volume = {542}, year = {2017}, month = {2017 Feb 09}, pages = {186-190}, abstract = {

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8\%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

}, issn = {1476-4687}, doi = {10.1038/nature21039}, author = {Marouli, Eirini and Graff, Mariaelisa and Medina-Gomez, Carolina and Ken Sin Lo and Andrew R Wood and Kjaer, Troels R and Fine, Rebecca S and Lu, Yingchang and Schurmann, Claudia and Highland, Heather M and R{\"u}eger, Sina and Thorleifsson, Gudmar and Justice, Anne E and Lamparter, David and Kathleen E Stirrups and Turcot, Val{\'e}rie and Young, Kristin L and Thomas W Winkler and T{\~o}nu Esko and Karaderi, Tugce and Locke, Adam E and Masca, Nicholas G D and Ng, Maggie C Y and Mudgal, Poorva and Rivas, Manuel A and Vedantam, Sailaja and Mahajan, Anubha and Guo, Xiuqing and Gon{\c c}alo R Abecasis and Aben, Katja K and Adair, Linda S and Alam, Dewan S and Albrecht, Eva and Allin, Kristine H and Matthew A. Allison and Amouyel, Philippe and Appel, Emil V and Arveiler, Dominique and Asselbergs, Folkert W and Auer, Paul L and Balkau, Beverley and Banas, Bernhard and Bang, Lia E and Benn, Marianne and Bergmann, Sven and Bielak, Lawrence F and Bl{\"u}her, Matthias and Boeing, Heiner and Boerwinkle, Eric and B{\"o}ger, Carsten A and Bonnycastle, Lori L and Bork-Jensen, Jette and Bots, Michiel L and Erwin P Bottinger and Bowden, Donald W and Brandslund, Ivan and Breen, Gerome and Brilliant, Murray H and Broer, Linda and Burt, Amber A and Adam S Butterworth and Carey, David J and Caulfield, Mark J and Chambers, John C and Daniel I Chasman and Yii-Der I Chen and Chowdhury, Rajiv and Cramer Christensen and Chu, Audrey Y and Cocca, Massimiliano and Collins, Francis S and Cook, James P and Corley, Janie and Jordi Corominas Galbany and Cox, Amanda J and Cuellar-Partida, Gabriel and Danesh, John and Gail Davies and de Bakker, Paul I W and de Borst, Gert J and de Denus, Simon and de Groot, Mark C H and de Mutsert, Ren{\'e}e and Ian J Deary and George Dedoussis and Ellen W Demerath and Anneke I den Hollander and Joe G Dennis and Di Angelantonio, Emanuele and Drenos, Fotios and Du, Mengmeng and Dunning, Alison M and Easton, Douglas F and Ebeling, Tapani and Edwards, Todd L and Ellinor, Patrick T and Elliott, Paul and Evangelou, Evangelos and Farmaki, Aliki-Eleni and Jessica Faul and Feitosa, Mary F and Feng, Shuang and Ferrannini, Ele and Marco M Ferrario and Ferri{\`e}res, Jean and Florez, Jose C and Ford, Ian and Myriam Fornage and Franks, Paul W and Frikke-Schmidt, Ruth and Galesloot, Tessel E and Gan, Wei and Gandin, Ilaria and Paolo P. Gasparini and Giedraitis, Vilmantas and Giri, Ayush and Giorgia G Girotto and Gordon, Scott D and Gordon-Larsen, Penny and Gorski, Mathias and Grarup, Niels and Grove, Megan L and Gudnason, Vilmundur and Gustafsson, Stefan and Hansen, Torben and Kathleen Mullan Harris and Tamara B Harris and Andrew T Hattersley and Caroline Hayward and He, Liang and Iris M Heid and Heikkil{\"a}, Kauko and Helgeland, {\O}yvind and Hernesniemi, Jussi and Hewitt, Alex W and Lynne J Hocking and Hollensted, Mette and Oddgeir L Holmen and Hovingh, G Kees and Howson, Joanna M M and Hoyng, Carel B and Huang, Paul L and Hveem, Kristian and Mohammed Arfan Ikram and Ingelsson, Erik and Jackson, Anne U and Jansson, Jan-H{\r a}kan and Jarvik, Gail P and Jensen, Gorm B and Jhun, Min A and Jia, Yucheng and Jiang, Xuejuan and Johansson, Stefan and J{\o}rgensen, Marit E and J{\o}rgensen, Torben and Jousilahti, Pekka and Jukema, J Wouter and Kahali, Bratati and Kahn, Ren{\'e} S and K{\"a}h{\"o}nen, Mika and Kamstrup, Pia R and Kanoni, Stavroula and Kaprio, Jaakko and Karaleftheri, Maria and Sharon L R Kardia and Karpe, Fredrik and Kee, Frank and Keeman, Renske and Lambertus A Kiemeney and Kitajima, Hidetoshi and Kluivers, Kirsten B and Kocher, Thomas and Komulainen, Pirjo and Kontto, Jukka and Kooner, Jaspal S and Charles Kooperberg and Kovacs, Peter and Kriebel, Jennifer and Kuivaniemi, Helena and K{\"u}ry, S{\'e}bastien and Kuusisto, Johanna and La Bianca, Martina and Laakso, Markku and Lakka, Timo A and Lange, Ethan M and Leslie A Lange and Langefeld, Carl D and Langenberg, Claudia and Eric B Larson and Lee, I-Te and Lehtim{\"a}ki, Terho and Lewis, Cora E and Li, Huaixing and Li, Jin and Li-Gao, Ruifang and Lin, Honghuang and Lin, Li-An and Lin, Xu and Lars Lind and Lindstr{\"o}m, Jaana and Linneberg, Allan and Liu, Yeheng and Yongmei Liu and Lophatananon, Artitaya and Luan, Jian{\textquoteright}an and Lubitz, Steven A and Lyytik{\"a}inen, Leo-Pekka and Mackey, David A and Pamela A F Madden and Alisa Manning and M{\"a}nnist{\"o}, Satu and Marenne, Ga{\"e}lle and Marten, Jonathan and Nicholas G Martin and Mazul, Angela L and Meidtner, Karina and Andres Metspalu and Mitchell, Paul and Mohlke, Karen L and Dennis O Mook-Kanamori and Morgan, Anna and Morris, Andrew D and Morris, Andrew P and M{\"u}ller-Nurasyid, Martina and Munroe, Patricia B and Michael A Nalls and Nauck, Matthias and Nelson, Christopher P and Neville, Matt and Sune Fallgaard Nielsen and Nikus, Kjell and Nj{\o}lstad, P{\r a}l R and B{\o}rge G Nordestgaard and Ntalla, Ioanna and Jeff O{\textquoteright}Connell and Oksa, Heikki and Loes M Olde Loohuis and Ophoff, Roel A and Owen, Katharine R and Packard, Chris J and Padmanabhan, Sandosh and Palmer, Colin N A and Pasterkamp, Gerard and Patel, Aniruddh P and Pattie, Alison and Pedersen, Oluf and Peissig, Peggy L and Peloso, Gina M and Pennell, Craig E and Markus Perola and Perry, James A and Perry, John R B and Person, Thomas N and Pirie, Ailith and Polasek, Ozren and Posthuma, Danielle and Olli T Raitakari and Rasheed, Asif and Rauramaa, Rainer and Reilly, Dermot F and Reiner, Alex P and Renstrom, Frida and Ridker, Paul M and Rioux, John D and Neil R Robertson and Robino, Antonietta and Rolandsson, Olov and Rudan, Igor and Ruth, Katherine S and Saleheen, Danish and Veikko Salomaa and Nilesh J Samani and Sandow, Kevin and Sapkota, Yadav and Sattar, Naveed and Schmidt, Marjanka K and Schreiner, Pamela J and Schulze, Matthias B and Scott, Robert A and Segura-Lepe, Marcelo P and Svati H Shah and Sim, Xueling and Sivapalaratnam, Suthesh and Small, Kerrin S and Albert Vernon Smith and Jennifer A Smith and Southam, Lorraine and Timothy Spector and Elizabeth K Speliotes and John M Starr and Steinthorsdottir, Valgerdur and Heather M Stringham and Stumvoll, Michael and Surendran, Praveen and {\textquoteright}t Hart, Leen M and Tansey, Katherine E and Tardif, Jean-Claude and Kent D Taylor and Teumer, Alexander and Thompson, Deborah J and Thorsteinsdottir, Unnur and Thuesen, Betina H and T{\"o}njes, Anke and Tromp, Gerard and Trompet, Stella and Tsafantakis, Emmanouil and Tuomilehto, Jaakko and Tybjaerg-Hansen, Anne and Tyrer, Jonathan P and Uher, Rudolf and Andr{\'e} G Uitterlinden and Ulivi, Sheila and van der Laan, Sander W and Van Der Leij, Andries R and Cornelia M van Duijn and van Schoor, Natasja M and van Setten, Jessica and Varbo, Anette and Varga, Tibor V and Varma, Rohit and Digna R Velez Edwards and Vermeulen, Sita H and Vestergaard, Henrik and Vitart, Veronique and Vogt, Thomas F and Vozzi, Diego and Walker, Mark and Wang, Feijie and Wang, Carol A and Wang, Shuai and Wang, Yiqin and Wareham, Nicholas J and Warren, Helen R and Wessel, Jennifer and Willems, Sara M and Wilson, James G and Daniel Witte and Woods, Michael O and Wu, Ying and Yaghootkar, Hanieh and Yao, Jie and Yao, Pang and Laura M Yerges-Armstrong and Young, Robin and Zeggini, Eleftheria and Zhan, Xiaowei and Zhang, Weihua and Jing Hua Zhao and Wei Zhao and Wei Zhao and Zheng, He and Zhou, Wei and Rotter, Jerome I and Boehnke, Michael and Kathiresan, Sekar and McCarthy, Mark I and Willer, Cristen J and Stefansson, Kari and Ingrid B Borecki and Liu, Dajiang J and Kari E North and Heard-Costa, Nancy L and Pers, Tune H and Lindgren, Cecilia M and Oxvig, Claus and Kutalik, Zolt{\'a}n and Fernando Rivadeneira and Ruth J F Loos and Timothy M Frayling and Joel N Hirschhron and Deloukas, Panos and Lettre, Guillaume} } @article {8882, title = {Genetic studies of body mass index yield new insights for obesity biology.}, journal = {Nature}, volume = {518}, year = {2015}, month = {2015 Feb 12}, pages = {197-206}, abstract = {

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P~<~5~{\texttimes}~10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for \~{}2.7\% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20\% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

}, keywords = {Age Factors, BMI, Continental Population Groups, Energy Metabolism, Europe, Female, Genome-Wide Association Study, Glutamic Acid, Humans, Insulin, Male, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Synapses}, issn = {1476-4687}, doi = {10.1038/nature14177}, author = {Locke, Adam E and Kahali, Bratati and Berndt, Sonja I and Justice, Anne E and Pers, Tune H and Day, Felix R and Powell, Corey and Vedantam, Sailaja and Buchkovich, Martin L and Yang, Jian and Croteau-Chonka, Damien C and T{\~o}nu Esko and Fall, Tove and Ferreira, Teresa and Gustafsson, Stefan and Kutalik, Zolt{\'a}n and Luan, Jian{\textquoteright}an and M{\"a}gi, Reedik and Randall, Joshua C and Thomas W Winkler and Andrew R Wood and Workalemahu, Tsegaselassie and Jessica Faul and Jennifer A Smith and Jing Hua Zhao and Wei Zhao and Chen, Jin and Rudolf Ferhmann and Hedman, {\r A}sa K and Karjalainen, Juha and Schmidt, Ellen M and Absher, Devin and Amin, Najaf and Anderson, Denise and Beekman, Marian and Bolton, Jennifer L and Bragg-Gresham, Jennifer L and Buyske, Steven and Demirkan, Ayse and Deng, Guohong and Georg B Ehret and Feenstra, Bjarke and Feitosa, Mary F and Fischer, Krista and Goel, Anuj and Gong, Jian and Jackson, Anne U and Kanoni, Stavroula and Kleber, Marcus E and Kristiansson, Kati and Lim, Unhee and Lotay, Vaneet and Mangino, Massimo and Irene Mateo Leach and Medina-Gomez, Carolina and Sarah E Medland and Michael A Nalls and Palmer, Cameron D and Pasko, Dorota and Pechlivanis, Sonali and Peters, Marjolein J and Prokopenko, Inga and Shungin, Dmitry and Stan{\v c}{\'a}kov{\'a}, Alena and Strawbridge, Rona J and Yun Ju Sung and Toshiko Tanaka and Teumer, Alexander and Trompet, Stella and van der Laan, Sander W and van Setten, Jessica and Jana V. van Vliet-Ostaptchouk and Wang, Zhaoming and Yengo, Loic and Zhang, Weihua and Isaacs, Aaron and Albrecht, Eva and {\"A}rnl{\"o}v, Johan and Arscott, Gillian M and Attwood, Antony P and Bandinelli, Stefania and Barrett, Amy and Bas, Isabelita N and Bellis, Claire and Bennett, Amanda J and Berne, Christian and Blagieva, Roza and Bl{\"u}her, Matthias and B{\"o}hringer, Stefan and Bonnycastle, Lori L and B{\"o}ttcher, Yvonne and Boyd, Heather A and Bruinenberg, Marcel and Caspersen, Ida H and Yii-Der I Chen and Robert Clark and Daw, E Warwick and de Craen, Anton J M and Delgado, Graciela and Dimitriou, Maria and Doney, Alex S F and Eklund, Niina and Estrada, Karol and Eury, Elodie and Folkersen, Lasse and Fraser, Ross M and Melissa E Garcia and Geller, Frank and Giedraitis, Vilmantas and Gigante, Bruna and Alan S Go and Golay, Alain and Goodall, Alison H and Gordon, Scott D and Gorski, Mathias and Hans-J{\"o}rgen Grabe and Grallert, Harald and Grammer, Tanja B and Gr{\"a}{\ss}ler, J{\"u}rgen and Gr{\"o}nberg, Henrik and Groves, Christopher J and Gusto, Ga{\"e}lle and Jeffrey Haessler and Hall, Per and Haller, Toomas and Hallmans, G{\"o}ran and Catharina A Hartman and Hassinen, Maija and Caroline Hayward and Heard-Costa, Nancy L and Helmer, Quinta and Hengstenberg, Christian and Oddgeir L Holmen and Jouke-Jan Hottenga and James, Alan L and Janina Jeff and Johansson, {\r A}sa and Jolley, Jennifer and Juliusdottir, Thorhildur and Kinnunen, Leena and Koenig, Wolfgang and Koskenvuo, Markku and Kratzer, Wolfgang and Laitinen, Jaana and Lamina, Claudia and Leander, Karin and Lee, Nanette R and Lichtner, Peter and Lars Lind and Lindstr{\"o}m, Jaana and Ken Sin Lo and Lobbens, St{\'e}phane and Lorbeer, Roberto and Lu, Yingchang and Mach, Fran{\c c}ois and Patrik K E Magnusson and Mahajan, Anubha and McArdle, Wendy L and McLachlan, Stela and Menni, Cristina and Merger, Sigrun and Mihailov, Evelin and Lili Milani and Moayyeri, Alireza and Monda, Keri L and Morken, Mario A and Mulas, Antonella and M{\"u}ller, Gabriele and M{\"u}ller-Nurasyid, Martina and Musk, Arthur W and Nagaraja, Ramaiah and Markus M N{\"o}then and Ilja M Nolte and Pilz, Stefan and Nigel W Rayner and Renstrom, Frida and Rettig, Rainer and Ried, Janina S and Ripke, Stephan and Neil R Robertson and Rose, Lynda M and Sanna, Serena and Scharnagl, Hubert and Scholtens, Salome and Schumacher, Fredrick R and Scott, William R and Seufferlein, Thomas and Jianxin Shi and Albert Vernon Smith and Smolonska, Joanna and Stanton, Alice V and Steinthorsdottir, Valgerdur and Kathleen E Stirrups and Heather M Stringham and Sundstr{\"o}m, Johan and Swertz, Morris A and Swift, Amy J and Syv{\"a}nen, Ann-Christine and Tan, Sian-Tsung and Bamidele O Tayo and Thorand, Barbara and Thorleifsson, Gudmar and Tyrer, Jonathan P and Uh, Hae-Won and Vandenput, Liesbeth and Verhulst, Frank C and Vermeulen, Sita H and Verweij, Niek and Vonk, Judith M and Lindsay L Waite and Warren, Helen R and Dawn M Waterworth and Michael N Weedon and Wilkens, Lynne R and Willenborg, Christina and Wilsgaard, Tom and Wojczynski, Mary K and Wong, Andrew and Alan F Wright and Zhang, Qunyuan and Brennan, Eoin P and Murim Choi and Dastani, Zari and Alexander W Drong and Eriksson, Per and Franco-Cereceda, Anders and G{\r a}din, Jesper R and Gharavi, Ali G and Goddard, Michael E and Handsaker, Robert E and Huang, Jinyan and Karpe, Fredrik and Kathiresan, Sekar and Keildson, Sarah and Kiryluk, Krzysztof and Kubo, Michiaki and Lee, Jong-Young and Liang, Liming and Lifton, Richard P and Ma, Baoshan and McCarroll, Steven A and McKnight, Amy J and Min, Josine L and Moffatt, Miriam F and Grant W Montgomery and Joanne M Murabito and Nicholson, George and Nyholt, Dale R and Okada, Yukinori and Perry, John R B and Dorajoo, Rajkumar and Reinmaa, Eva and Salem, Rany M and Sandholm, Niina and Scott, Robert A and Stolk, Lisette and Takahashi, Atsushi and Tanaka, Toshihiro and Ferdinand M van {\textquoteright}t Hooft and Anna A E Vinkhuyzen and Westra, Harm-Jan and Wei Zhang and Krina T Zondervan and Andrew C Heath and Arveiler, Dominique and Bakker, Stephan J L and Beilby, John and Bergman, Richard N and Blangero, John and Bovet, Pascal and Campbell, Harry and Caulfield, Mark J and Cesana, Giancarlo and Chakravarti, Aravinda and Daniel I Chasman and Chines, Peter S and Collins, Francis S and Crawford, Dana C and Cupples, L Adrienne and Cusi, Daniele and Danesh, John and de Faire, Ulf and Hester M den Ruijter and Dominiczak, Anna F and Erbel, Raimund and Erdmann, Jeanette and Johan G Eriksson and Farrall, Martin and Felix, Stephan B and Ferrannini, Ele and Ferri{\`e}res, Jean and Ford, Ian and Forouhi, Nita G and Forrester, Terrence and Franco, Oscar H and Gansevoort, Ron T and Gejman, Pablo V and Gieger, Christian and Gottesman, Omri and Gudnason, Vilmundur and Gyllensten, Ulf and Hall, Alistair S and Tamara B Harris and Andrew T Hattersley and Hicks, Andrew A and Hindorff, Lucia A and Aroon Hingorani and Hofman, Albert and Homuth, Georg and Hovingh, G Kees and Humphries, Steve E and Hunt, Steven C and Hypp{\"o}nen, Elina and Illig, Thomas and Jacobs, Kevin B and J{\"a}rvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Johansen, Berit and Jousilahti, Pekka and Jukema, J Wouter and Jula, Antti M and Kaprio, Jaakko and Kastelein, John J P and Keinanen-Kiukaanniemi, Sirkka M and Lambertus A Kiemeney and Knekt, Paul and Kooner, Jaspal S and Charles Kooperberg and Kovacs, Peter and Kraja, Aldi T and Kumari, Meena and Kuusisto, Johanna and Lakka, Timo A and Langenberg, Claudia and Loic Le Marchand and Lehtim{\"a}ki, Terho and Lyssenko, Valeriya and M{\"a}nnist{\"o}, Satu and Marette, Andr{\'e} and Matise, Tara C and McKenzie, Colin A and McKnight, Barbara and Moll, Frans L and Morris, Andrew D and Morris, Andrew P and Murray, Jeffrey C and Nelis, Mari and Ohlsson, Claes and Oldehinkel, Albertine J and Ong, Ken K and Pamela A F Madden and Pasterkamp, Gerard and Peden, John F and Peters, Annette and Postma, Dirkje S and Pramstaller, Peter P and Price, Jackie F and Qi, Lu and Olli T Raitakari and Rankinen, Tuomo and Rao, D C and Rice, Treva K and Ridker, Paul M and Rioux, John D and Ritchie, Marylyn D and Rudan, Igor and Veikko Salomaa and Nilesh J Samani and Saramies, Jouko and Sarzynski, Mark A and Schunkert, Heribert and Schwarz, Peter E H and Peter Sever and Alan R Shuldiner and Sinisalo, Juha and Stolk, Ronald P and Strauch, Konstantin and T{\"o}njes, Anke and Tr{\'e}gou{\"e}t, David-Alexandre and Tremblay, Angelo and Tremoli, Elena and Virtamo, Jarmo and Vohl, Marie-Claude and V{\"o}lker, Uwe and Waeber, G{\'e}rard and Gonneke Willemsen and Witteman, Jacqueline C and Zillikens, M Carola and Adair, Linda S and Amouyel, Philippe and Asselbergs, Folkert W and Assimes, Themistocles L and Bochud, Murielle and Boehm, Bernhard O and Boerwinkle, Eric and Bornstein, Stefan R and Erwin P Bottinger and Bouchard, Claude and Cauchi, St{\'e}phane and Chambers, John C and Chanock, Stephen J and Cooper, Richard S and de Bakker, Paul I W and George Dedoussis and Luigi Ferrucci and Franks, Paul W and Froguel, Philippe and Leif C Groop and Christopher A Haiman and Hamsten, Anders and Hui, Jennie and Hunter, David J and Hveem, Kristian and Kaplan, Robert C and Mika Kivim{\"a}ki and Kuh, Diana and Laakso, Markku and Yongmei Liu and Nicholas G Martin and M{\"a}rz, Winfried and Melbye, Mads and Andres Metspalu and Moebus, Susanne and Munroe, Patricia B and Nj{\o}lstad, Inger and Ben A Oostra and Palmer, Colin N A and Nancy L Pedersen and Markus Perola and P{\'e}russe, Louis and Peters, Ulrike and Power, Chris and Quertermous, Thomas and Rauramaa, Rainer and Fernando Rivadeneira and Saaristo, Timo E and Saleheen, Danish and Sattar, Naveed and Eric E Schadt and Schlessinger, David and Eline P Slagboom and Snieder, Harold and Timothy Spector and Thorsteinsdottir, Unnur and Stumvoll, Michael and Tuomilehto, Jaakko and Andr{\'e} G Uitterlinden and Uusitupa, Matti and van der Harst, Pim and Walker, Mark and Wallaschofski, Henri and Wareham, Nicholas J and Watkins, Hugh and David R Weir and Wichmann, H-Erich and James F Wilson and Zanen, Pieter and Ingrid B Borecki and Deloukas, Panos and Caroline S Fox and Iris M Heid and Jeff O{\textquoteright}Connell and David P Strachan and Stefansson, Kari and Cornelia M van Duijn and Gon{\c c}alo R Abecasis and Lude L Franke and Timothy M Frayling and McCarthy, Mark I and Peter M Visscher and Scherag, Andre and Willer, Cristen J and Boehnke, Michael and Mohlke, Karen L and Lindgren, Cecilia M and Beckmann, Jacques S and Barroso, In{\^e}s and Kari E North and Ingelsson, Erik and Joel N Hirschhron and Ruth J F Loos and Elizabeth K Speliotes} }