TY - JOUR
T1 - Additive effects of obesity and loneliness on C-reactive protein.
JF - PLoS One
Y1 - 2018
A1 - Gregory Pavela
A1 - Kim, Young-Il
A1 - Salvy, Sarah-Jeanne
KW - Biomarkers
KW - BMI
KW - C-reactive protein
KW - Depressive symptoms
KW - Loneliness
AB - Obesity and loneliness are associated with C-reactive protein (CRP), a predictor of cardiovascular disease. It is unknown whether the co-presence of obesity and loneliness is associated with additional risk for clinically elevated CRP. The present study thus examines their independent and combined effects on elevated CRP in older adults. Data come from 10,912 respondents who completed the 2008 and 2010 waves of the Health and Retirement Study. Loneliness was measured using an 11-item Loneliness Scale and body mass index was calculated from technician measured height and weight. Our primary outcome is high sensitivity CRP (hsCRP). Survey-weighted logistic regression models were used to test whether loneliness and BMI category are independent predictors of CRP after adjusting for demographics and other inflammatory-related covariates. In the fully adjusted model for men, obesity (OR = 2.36, p < .0001) was associated with increased odds of hsCRP >3.0. Among females, being overweight (OR = 1.75, p < .0001) or obese (OR = 4.01, p < .0001) were associated increased odds of hsCRP>3.0. Among both men and women, results from fully adjusted models indicated that loneliness was not associated with clinically elevated hsCRP (OR = 1.34, p = .0535; OR = 0.97, p = 0.6776, respectively).
VL - 13
IS - 11
U1 - http://www.ncbi.nlm.nih.gov/pubmed/30439985?dopt=Abstract
ER -
TY - JOUR
T1 - Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry.
JF - Human Molecular Genetics
Y1 - 2018
A1 - Yengo, Loic
A1 - Sidorenko, Julia
A1 - Kathryn E Kemper
A1 - Zheng, Zhili
A1 - Andrew R Wood
A1 - Michael N Weedon
A1 - Timothy M Frayling
A1 - Joel N Hirschhron
A1 - Yang, Jian
A1 - Peter M Visscher
KW - BMI
KW - Genetics
KW - GWAS
KW - Height
AB - Recent genome-wide association studies (GWAS) of height and body mass index (BMI) in ∼250000 European participants have led to the discovery of ∼700 and ∼100 nearly independent single nucleotide polymorphisms (SNPs) associated with these traits, respectively. Here we combine summary statistics from those two studies with GWAS of height and BMI performed in ∼450000 UK Biobank participants of European ancestry. Overall, our combined GWAS meta-analysis reaches N ∼700000 individuals and substantially increases the number of GWAS signals associated with these traits. We identified 3290 and 941 near-independent SNPs associated with height and BMI, respectively (at a revised genome-wide significance threshold of P < 1 × 10-8), including 1185 height-associated SNPs and 751 BMI-associated SNPs located within loci not previously identified by these two GWAS. The near-independent genome-wide significant SNPs explain ∼24.6% of the variance of height and ∼6.0% of the variance of BMI in an independent sample from the Health and Retirement Study (HRS). Correlations between polygenic scores based upon these SNPs with actual height and BMI in HRS participants were ∼0.44 and ∼0.22, respectively. From analyses of integrating GWAS and expression quantitative trait loci (eQTL) data by summary-data-based Mendelian randomization, we identified an enrichment of eQTLs among lead height and BMI signals, prioritizing 610 and 138 genes, respectively. Our study demonstrates that, as previously predicted, increasing GWAS sample sizes continues to deliver, by the discovery of new loci, increasing prediction accuracy and providing additional data to achieve deeper insight into complex trait biology. All summary statistics are made available for follow-up studies.
VL - 27
IS - 20
U1 - http://www.ncbi.nlm.nih.gov/pubmed/30124842?dopt=Abstract
ER -
TY - JOUR
T1 - Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry
JF - Human Molecular Genetics
Y1 - 2018
A1 - Yengo, Loic
A1 - Sidorenko, Julia
A1 - Kathryn E Kemper
A1 - Zheng, Zhili
A1 - Andrew R Wood
A1 - Michael N Weedon
A1 - Timothy M Frayling
A1 - Joel N Hirschhron
A1 - Yang, Jian
A1 - Peter M Visscher
KW - BMI
KW - Genetics
KW - GWAS
KW - Height
AB - Recent genome-wide association studies (GWAS) of height and body mass index (BMI) in similar to 250000 European participants have led to the discovery of similar to 700 and similar to 100 nearly independent single nucleotide polymorphisms (SNPs) associated with these traits, respectively. Here we combine summary statistics from those two studies with GWAS of height and BMI performed in similar to 450000 UK Biobank participants of European ancestry. Overall, our combined GWAS meta-analysis reaches N similar to 700000 individuals and substantially increases the number of GWAS signals associated with these traits. We identified 3290 and 941 near-independent SNPs associated with height and BMI, respectively (at a revised genome-wide significance threshold of P < 1 x 10(-8)), including 1185 height-associated SNPs and 751 BMI-associated SNPs located within loci not previously identified by these two GWAS. The near-independent genome-wide significant SNPs explain similar to 24.6% of the variance of height and similar to 6.0% of the variance of BMI in an independent sample from the Health and Retirement Study (HRS). Correlations between polygenic scores based upon these SNPs with actual height and BMI in HRS participants were similar to 0.44 and similar to 0.22, respectively. From analyses of integrating GWAS and expression quantitative trait loci (eQTL) data by summary-data-based Mendelian randomization, we identified an enrichment of eQTLs among lead height and BMI signals, prioritizing 610 and 138 genes, respectively. Our study demonstrates that, as previously predicted, increasing GWAS sample sizes continues to deliver, by the discovery of new loci, increasing prediction accuracy and providing additional data to achieve deeper insight into complex trait biology. All summary statistics are made available for follow-up studies.
VL - 27
IS - 20
ER -
TY - JOUR
T1 - Interaction between Social/Psychosocial Factors and Genetic Variants on Body Mass Index: A Gene-Environment Interaction Analysis in a Longitudinal Setting
JF - International Journal of Environmental Research and Public Health
Y1 - 2017
A1 - Wei Zhao
A1 - Erin B Ware
A1 - He, Zihuai
A1 - Sharon L R Kardia
A1 - Jessica D Faul
KW - BMI
KW - Genetics
KW - Obesity
AB - Obesity, which develops over time, is one of the leading causes of chronic diseases such as cardiovascular disease. However, hundreds of BMI (body mass index)-associated genetic loci identified through large-scale genome-wide association studies (GWAS) only explain about 2.7% of BMI variation. Most common human traits are believed to be influenced by both genetic and environmental factors. Past studies suggest a variety of environmental features that are associated with obesity, including socioeconomic status and psychosocial factors. This study combines both gene/regions and environmental factors to explore whether social/psychosocial factors (childhood and adult socioeconomic status, social support, anger, chronic burden, stressful life events, and depressive symptoms) modify the effect of sets of genetic variants on BMI in European American and African American participants in the Health and Retirement Study (HRS). In order to incorporate longitudinal phenotype data collected in the HRS and investigate entire sets of single nucleotide polymorphisms (SNPs) within gene/region simultaneously, we applied a novel set-based test for gene-environment interaction in longitudinal studies (LGEWIS). Childhood socioeconomic status (parental education) was found to modify the genetic effect in the gene/region around SNP rs9540493 on BMI in European Americans in the HRS. The most significant SNP (rs9540488) by childhood socioeconomic status interaction within the rs9540493 gene/region was suggestively replicated in the Multi-Ethnic Study of Atherosclerosis (MESA) (p = 0.07).
VL - 14
UR - http://www.mdpi.com/1660-4601/14/10/1153http://www.mdpi.com/1660-4601/14/10/1153/pdf
IS - 10
JO - IJERPH
ER -
TY - JOUR
T1 - Genetic studies of body mass index yield new insights for obesity biology.
JF - Nature
Y1 - 2015
A1 - Locke, Adam E
A1 - Kahali, Bratati
A1 - Berndt, Sonja I
A1 - Justice, Anne E
A1 - Pers, Tune H
A1 - Day, Felix R
A1 - Powell, Corey
A1 - Vedantam, Sailaja
A1 - Buchkovich, Martin L
A1 - Yang, Jian
A1 - Croteau-Chonka, Damien C
A1 - Tõnu Esko
A1 - Fall, Tove
A1 - Ferreira, Teresa
A1 - Gustafsson, Stefan
A1 - Kutalik, Zoltán
A1 - Luan, Jian'an
A1 - Mägi, Reedik
A1 - Randall, Joshua C
A1 - Winkler, Thomas W
A1 - Andrew R Wood
A1 - Workalemahu, Tsegaselassie
A1 - Jessica D Faul
A1 - Jennifer A Smith
A1 - Jing Hua Zhao
A1 - Wei Zhao
A1 - Chen, Jin
A1 - Rudolf Ferhmann
A1 - Hedman, Åsa K
A1 - Karjalainen, Juha
A1 - Schmidt, Ellen M
A1 - Absher, Devin
A1 - Amin, Najaf
A1 - Anderson, Denise
A1 - Beekman, Marian
A1 - Bolton, Jennifer L
A1 - Bragg-Gresham, Jennifer L
A1 - Buyske, Steven
A1 - Demirkan, Ayse
A1 - Deng, Guohong
A1 - Georg B Ehret
A1 - Feenstra, Bjarke
A1 - Feitosa, Mary F
A1 - Fischer, Krista
A1 - Goel, Anuj
A1 - Gong, Jian
A1 - Jackson, Anne U
A1 - Kanoni, Stavroula
A1 - Kleber, Marcus E
A1 - Kristiansson, Kati
A1 - Lim, Unhee
A1 - Lotay, Vaneet
A1 - Mangino, Massimo
A1 - Irene Mateo Leach
A1 - Medina-Gomez, Carolina
A1 - Sarah E Medland
A1 - Michael A Nalls
A1 - Palmer, Cameron D
A1 - Pasko, Dorota
A1 - Pechlivanis, Sonali
A1 - Peters, Marjolein J
A1 - Prokopenko, Inga
A1 - Shungin, Dmitry
A1 - Stančáková, Alena
A1 - Strawbridge, Rona J
A1 - Yun Ju Sung
A1 - Toshiko Tanaka
A1 - Teumer, Alexander
A1 - Trompet, Stella
A1 - van der Laan, Sander W
A1 - van Setten, Jessica
A1 - Jana V. van Vliet-Ostaptchouk
A1 - Wang, Zhaoming
A1 - Yengo, Loic
A1 - Zhang, Weihua
A1 - Isaacs, Aaron
A1 - Albrecht, Eva
A1 - Ärnlöv, Johan
A1 - Arscott, Gillian M
A1 - Attwood, Antony P
A1 - Bandinelli, Stefania
A1 - Barrett, Amy
A1 - Bas, Isabelita N
A1 - Bellis, Claire
A1 - Bennett, Amanda J
A1 - Berne, Christian
A1 - Blagieva, Roza
A1 - Blüher, Matthias
A1 - Böhringer, Stefan
A1 - Bonnycastle, Lori L
A1 - Böttcher, Yvonne
A1 - Boyd, Heather A
A1 - Bruinenberg, Marcel
A1 - Caspersen, Ida H
A1 - Yii-Der I Chen
A1 - Robert Clark
A1 - Daw, E Warwick
A1 - de Craen, Anton J M
A1 - Delgado, Graciela
A1 - Dimitriou, Maria
A1 - Doney, Alex S F
A1 - Eklund, Niina
A1 - Estrada, Karol
A1 - Eury, Elodie
A1 - Folkersen, Lasse
A1 - Fraser, Ross M
A1 - Melissa E Garcia
A1 - Geller, Frank
A1 - Giedraitis, Vilmantas
A1 - Gigante, Bruna
A1 - Alan S Go
A1 - Golay, Alain
A1 - Goodall, Alison H
A1 - Gordon, Scott D
A1 - Gorski, Mathias
A1 - Grabe, Hans-Jörgen
A1 - Grallert, Harald
A1 - Grammer, Tanja B
A1 - Gräßler, Jürgen
A1 - Grönberg, Henrik
A1 - Groves, Christopher J
A1 - Gusto, Gaëlle
A1 - Jeffrey Haessler
A1 - Hall, Per
A1 - Haller, Toomas
A1 - Hallmans, Göran
A1 - Catharina A Hartman
A1 - Hassinen, Maija
A1 - Caroline Hayward
A1 - Heard-Costa, Nancy L
A1 - Helmer, Quinta
A1 - Hengstenberg, Christian
A1 - Oddgeir L Holmen
A1 - Jouke-Jan Hottenga
A1 - James, Alan L
A1 - Jeff, Janina M
A1 - Johansson, Åsa
A1 - Jolley, Jennifer
A1 - Juliusdottir, Thorhildur
A1 - Kinnunen, Leena
A1 - Koenig, Wolfgang
A1 - Koskenvuo, Markku
A1 - Kratzer, Wolfgang
A1 - Laitinen, Jaana
A1 - Lamina, Claudia
A1 - Leander, Karin
A1 - Lee, Nanette R
A1 - Lichtner, Peter
A1 - Lars Lind
A1 - Lindström, Jaana
A1 - Ken Sin Lo
A1 - Lobbens, Stéphane
A1 - Lorbeer, Roberto
A1 - Lu, Yingchang
A1 - Mach, François
A1 - Patrik K E Magnusson
A1 - Mahajan, Anubha
A1 - McArdle, Wendy L
A1 - McLachlan, Stela
A1 - Menni, Cristina
A1 - Merger, Sigrun
A1 - Mihailov, Evelin
A1 - Lili Milani
A1 - Moayyeri, Alireza
A1 - Monda, Keri L
A1 - Morken, Mario A
A1 - Mulas, Antonella
A1 - Müller, Gabriele
A1 - Müller-Nurasyid, Martina
A1 - Musk, Arthur W
A1 - Nagaraja, Ramaiah
A1 - Markus M Nöthen
A1 - Ilja M Nolte
A1 - Pilz, Stefan
A1 - Rayner, Nigel W
A1 - Renstrom, Frida
A1 - Rettig, Rainer
A1 - Ried, Janina S
A1 - Ripke, Stephan
A1 - Neil R Robertson
A1 - Rose, Lynda M
A1 - Sanna, Serena
A1 - Scharnagl, Hubert
A1 - Scholtens, Salome
A1 - Schumacher, Fredrick R
A1 - Scott, William R
A1 - Seufferlein, Thomas
A1 - Jianxin Shi
A1 - Albert Vernon Smith
A1 - Smolonska, Joanna
A1 - Stanton, Alice V
A1 - Steinthorsdottir, Valgerdur
A1 - Kathleen E Stirrups
A1 - Stringham, Heather M
A1 - Sundström, Johan
A1 - Swertz, Morris A
A1 - Swift, Amy J
A1 - Syvänen, Ann-Christine
A1 - Tan, Sian-Tsung
A1 - Bamidele O Tayo
A1 - Thorand, Barbara
A1 - Thorleifsson, Gudmar
A1 - Tyrer, Jonathan P
A1 - Uh, Hae-Won
A1 - Vandenput, Liesbeth
A1 - Verhulst, Frank C
A1 - Vermeulen, Sita H
A1 - Verweij, Niek
A1 - Vonk, Judith M
A1 - Lindsay L Waite
A1 - Warren, Helen R
A1 - Dawn M Waterworth
A1 - Michael N Weedon
A1 - Wilkens, Lynne R
A1 - Willenborg, Christina
A1 - Wilsgaard, Tom
A1 - Wojczynski, Mary K
A1 - Wong, Andrew
A1 - Alan F Wright
A1 - Zhang, Qunyuan
A1 - Brennan, Eoin P
A1 - Murim Choi
A1 - Dastani, Zari
A1 - Alexander W Drong
A1 - Eriksson, Per
A1 - Franco-Cereceda, Anders
A1 - Gådin, Jesper R
A1 - Gharavi, Ali G
A1 - Goddard, Michael E
A1 - Handsaker, Robert E
A1 - Huang, Jinyan
A1 - Karpe, Fredrik
A1 - Kathiresan, Sekar
A1 - Keildson, Sarah
A1 - Kiryluk, Krzysztof
A1 - Kubo, Michiaki
A1 - Lee, Jong-Young
A1 - Liang, Liming
A1 - Lifton, Richard P
A1 - Ma, Baoshan
A1 - McCarroll, Steven A
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A1 - Min, Josine L
A1 - Moffatt, Miriam F
A1 - Grant W Montgomery
A1 - Joanne M Murabito
A1 - Nicholson, George
A1 - Nyholt, Dale R
A1 - Okada, Yukinori
A1 - Perry, John R B
A1 - Dorajoo, Rajkumar
A1 - Reinmaa, Eva
A1 - Salem, Rany M
A1 - Sandholm, Niina
A1 - Scott, Robert A
A1 - Stolk, Lisette
A1 - Takahashi, Atsushi
A1 - Tanaka, Toshihiro
A1 - Ferdinand M van 't Hooft
A1 - Anna A E Vinkhuyzen
A1 - Westra, Harm-Jan
A1 - Wei Zhang
A1 - Krina T Zondervan
A1 - Heath, Andrew C
A1 - Arveiler, Dominique
A1 - Bakker, Stephan J L
A1 - Beilby, John
A1 - Bergman, Richard N
A1 - Blangero, John
A1 - Bovet, Pascal
A1 - Campbell, Harry
A1 - Caulfield, Mark J
A1 - Cesana, Giancarlo
A1 - Chakravarti, Aravinda
A1 - Chasman, Daniel I
A1 - Chines, Peter S
A1 - Collins, Francis S
A1 - Crawford, Dana C
A1 - Cupples, L Adrienne
A1 - Cusi, Daniele
A1 - Danesh, John
A1 - de Faire, Ulf
A1 - Hester M den Ruijter
A1 - Dominiczak, Anna F
A1 - Erbel, Raimund
A1 - Erdmann, Jeanette
A1 - Johan G. Eriksson
A1 - Farrall, Martin
A1 - Felix, Stephan B
A1 - Ferrannini, Ele
A1 - Ferrières, Jean
A1 - Ford, Ian
A1 - Forouhi, Nita G
A1 - Forrester, Terrence
A1 - Franco, Oscar H
A1 - Gansevoort, Ron T
A1 - Gejman, Pablo V
A1 - Gieger, Christian
A1 - Gottesman, Omri
A1 - Gudnason, Vilmundur
A1 - Gyllensten, Ulf
A1 - Hall, Alistair S
A1 - Tamara B Harris
A1 - Hattersley, Andrew T
A1 - Hicks, Andrew A
A1 - Hindorff, Lucia A
A1 - Hingorani, Aroon D
A1 - Hofman, Albert
A1 - Homuth, Georg
A1 - Hovingh, G Kees
A1 - Humphries, Steve E
A1 - Hunt, Steven C
A1 - Hyppönen, Elina
A1 - Illig, Thomas
A1 - Jacobs, Kevin B
A1 - Järvelin, Marjo-Riitta
A1 - Jöckel, Karl-Heinz
A1 - Johansen, Berit
A1 - Jousilahti, Pekka
A1 - Jukema, J Wouter
A1 - Jula, Antti M
A1 - Kaprio, Jaakko
A1 - Kastelein, John J P
A1 - Keinanen-Kiukaanniemi, Sirkka M
A1 - Lambertus A Kiemeney
A1 - Knekt, Paul
A1 - Kooner, Jaspal S
A1 - Kooperberg, Charles
A1 - Kovacs, Peter
A1 - Kraja, Aldi T
A1 - Kumari, Meena
A1 - Kuusisto, Johanna
A1 - Lakka, Timo A
A1 - Langenberg, Claudia
A1 - Loic Le Marchand
A1 - Lehtimäki, Terho
A1 - Lyssenko, Valeriya
A1 - Männistö, Satu
A1 - Marette, André
A1 - Matise, Tara C
A1 - McKenzie, Colin A
A1 - McKnight, Barbara
A1 - Moll, Frans L
A1 - Morris, Andrew D
A1 - Morris, Andrew P
A1 - Murray, Jeffrey C
A1 - Nelis, Mari
A1 - Ohlsson, Claes
A1 - Oldehinkel, Albertine J
A1 - Ong, Ken K
A1 - Pamela A F Madden
A1 - Pasterkamp, Gerard
A1 - Peden, John F
A1 - Peters, Annette
A1 - Postma, Dirkje S
A1 - Pramstaller, Peter P
A1 - Price, Jackie F
A1 - Qi, Lu
A1 - Olli T Raitakari
A1 - Rankinen, Tuomo
A1 - Rao, D C
A1 - Rice, Treva K
A1 - Ridker, Paul M
A1 - Rioux, John D
A1 - Ritchie, Marylyn D
A1 - Rudan, Igor
A1 - Veikko Salomaa
A1 - Nilesh J Samani
A1 - Saramies, Jouko
A1 - Sarzynski, Mark A
A1 - Schunkert, Heribert
A1 - Schwarz, Peter E H
A1 - Sever, Peter
A1 - Alan R Shuldiner
A1 - Sinisalo, Juha
A1 - Stolk, Ronald P
A1 - Strauch, Konstantin
A1 - Tönjes, Anke
A1 - Trégouët, David-Alexandre
A1 - Tremblay, Angelo
A1 - Tremoli, Elena
A1 - Virtamo, Jarmo
A1 - Vohl, Marie-Claude
A1 - Völker, Uwe
A1 - Waeber, Gérard
A1 - Gonneke Willemsen
A1 - Witteman, Jacqueline C
A1 - Zillikens, M Carola
A1 - Adair, Linda S
A1 - Amouyel, Philippe
A1 - Asselbergs, Folkert W
A1 - Assimes, Themistocles L
A1 - Bochud, Murielle
A1 - Boehm, Bernhard O
A1 - Boerwinkle, Eric
A1 - Bornstein, Stefan R
A1 - Erwin P Bottinger
A1 - Bouchard, Claude
A1 - Cauchi, Stéphane
A1 - Chambers, John C
A1 - Chanock, Stephen J
A1 - Cooper, Richard S
A1 - de Bakker, Paul I W
A1 - George Dedoussis
A1 - Luigi Ferrucci
A1 - Franks, Paul W
A1 - Froguel, Philippe
A1 - Groop, Leif C
A1 - Haiman, Christopher A
A1 - Hamsten, Anders
A1 - Hui, Jennie
A1 - Hunter, David J
A1 - Hveem, Kristian
A1 - Kaplan, Robert C
A1 - Mika Kivimäki
A1 - Kuh, Diana
A1 - Laakso, Markku
A1 - Yongmei Liu
A1 - Nicholas G Martin
A1 - März, Winfried
A1 - Melbye, Mads
A1 - Andres Metspalu
A1 - Moebus, Susanne
A1 - Munroe, Patricia B
A1 - Njølstad, Inger
A1 - Ben A Oostra
A1 - Palmer, Colin N A
A1 - Nancy L Pedersen
A1 - Markus Perola
A1 - Pérusse, Louis
A1 - Peters, Ulrike
A1 - Power, Chris
A1 - Quertermous, Thomas
A1 - Rauramaa, Rainer
A1 - Fernando Rivadeneira
A1 - Saaristo, Timo E
A1 - Saleheen, Danish
A1 - Sattar, Naveed
A1 - Schadt, Eric E
A1 - Schlessinger, David
A1 - Eline P Slagboom
A1 - Snieder, Harold
A1 - Tim D Spector
A1 - Thorsteinsdottir, Unnur
A1 - Stumvoll, Michael
A1 - Tuomilehto, Jaakko
A1 - André G Uitterlinden
A1 - Uusitupa, Matti
A1 - van der Harst, Pim
A1 - Walker, Mark
A1 - Wallaschofski, Henri
A1 - Wareham, Nicholas J
A1 - Watkins, Hugh
A1 - David R Weir
A1 - Wichmann, H-Erich
A1 - James F Wilson
A1 - Zanen, Pieter
A1 - Ingrid B Borecki
A1 - Deloukas, Panos
A1 - Fox, Caroline S
A1 - Heid, Iris M
A1 - O'Connell, Jeffrey R
A1 - Strachan, David P
A1 - Stefansson, Kari
A1 - Cornelia M van Duijn
A1 - Gonçalo R Abecasis
A1 - Lude L Franke
A1 - Timothy M Frayling
A1 - McCarthy, Mark I
A1 - Peter M Visscher
A1 - Scherag, Andre
A1 - Willer, Cristen J
A1 - Boehnke, Michael
A1 - Mohlke, Karen L
A1 - Lindgren, Cecilia M
A1 - Beckmann, Jacques S
A1 - Barroso, Inês
A1 - North, Kari E
A1 - Ingelsson, Erik
A1 - Joel N Hirschhron
A1 - Ruth J F Loos
A1 - Speliotes, Elizabeth K
KW - Age Factors
KW - BMI
KW - Continental Population Groups
KW - Energy Metabolism
KW - Europe
KW - Female
KW - Genome-Wide Association Study
KW - Glutamic Acid
KW - Humans
KW - Insulin
KW - Male
KW - Obesity
KW - Polymorphism, Single Nucleotide
KW - Quantitative Trait Loci
KW - Synapses
AB - 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 × 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.

VL - 518
IS - 7538
U1 - http://www.ncbi.nlm.nih.gov/pubmed/25673413?dopt=Abstract
ER -