Person: Qi, Lu
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Publication Fat Mass–and Obesity-Associated (FTO) Gene Variant Is Associated With Obesity
(American Diabetes Association, 2008) Qi, Lu; Kang, Kihwa; Zhang, Cuilin; Van Dam, Rob; Kraft, Peter; Hunter, David; Lee, Chih-Hao; Hu, FrankOBJECTIVE—To examine the longitudinal association of fat mass–and obesity-associated (FTO) variant with obesity, circulating adipokine levels, and FTO expression in various materials from human and mouse. RESEARCH DESIGN AND METHODS—We genotyped rs9939609 in 2,287 men and 3,520 women from two prospective cohorts. Plasma adiponectin and leptin were measured in a subset of diabetic men (n = 854) and women (n = 987). Expression of FTO was tested in adipocytes from db/db mice and mouse macrophages. RESULTS—We observed a trend toward decreasing associations between rs9939609 and BMI at older age (≥65 years) in men, whereas the associations were constant across different age groups in women. In addition, the single nucleotide polymorphism (SNP) rs9939609 was associated with lower plasma adiponectin (log[e]− means, 1.82 ± 0.04, 1.73 ± 0.03, and 1.68 ± 0.05 for TT, TA, and AA genotypes, respectively; P for trend = 0.02) and leptin (log[e]− means, 3.56 ± 0.04, 3.63 ± 0.04, and 3.70 ± 0.06; P for trend = 0.06) in diabetic women. Adjustment for BMI attenuated the associations. FTO gene was universally expressed in human and mice tissues, including adipocytes. In an ancillary study of adipocytes from db/db mice, FTO expression was ∼50% lower than in those from wild-type mice. CONCLUSIONS—The association between FTO SNP rs9939609 and obesity risk may decline at older age. The variant affects circulating adiponectin and leptin levels through the changes in BMI. In addition, the expression of FTO gene was reduced in adipocytes from db/db mice.
Publication Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution
(Public Library of Science, 2009) Lindgren, Cecilia M.; Heid, Iris M.; Randall, Joshua C.; Lamina, Claudia; Steinthorsdottir, Valgerdur; Speliotes, Elizabeth K.; Thorleifsson, Gudmar; Willer, Cristen J.; Herrera, Blanca M.; Jackson, Anne U.; Lim, Noha; Scheet, Paul; Soranzo, Nicole; Amin, Najaf; Aulchenko, Yurii S.; Chambers, John C.; Drong, Alexander; Luan, Jian'an; Rivadeneira, Fernando; Sanna, Serena; Timpson, Nicholas J.; Zillikens, M. Carola; Almgren, Peter; Bandinelli, Stefania; Bennett, Amanda J.; Bergman, Richard N.; Bonnycastle, Lori L.; Bumpstead, Suzannah J.; Chanock, Stephen J.; Cherkas, Lynn; Chines, Peter; Coin, Lachlan; Cooper, Cyrus; Crawford, Gabriel; Doering, Angela; Dominiczak, Anna; Doney, Alex S. F.; Ebrahim, Shah; Elliott, Paul; Erdos, Michael R.; Estrada, Karol; Ferrucci, Luigi; Fischer, Guido; Forouhi, Nita G.; Gieger, Christian; Grallert, Harald; Groves, Christopher J.; Grundy, Scott; Guiducci, Candace; Hadley, David; Hamsten, Anders; Havulinna, Aki S.; Holle, Rolf; Holloway, John W.; Illig, Thomas; Isomaa, Bo; Jacobs, Leonie C.; Jameson, Karen; Jousilahti, Pekka; Karpe, Fredrik; Kuusisto, Johanna; Laitinen, Jaana; Lathrop, G. Mark; Lawlor, Debbie A.; Mangino, Massimo; McArdle, Wendy L.; Meitinger, Thomas; Morken, Mario A.; Morris, Andrew P.; Munroe, Patricia; Narisu, Narisu; Nordström, Anna; Nordström, Peter; Oostra, Ben A.; Palmer, Colin N. A.; Payne, Felicity; Peden, John F.; Prokopenko, Inga; Renström, Frida; Ruokonen, Aimo; Salomaa, Veikko; Sandhu, Manjinder S.; Scuteri, Angelo; Silander, Kaisa; Song, Kijoung; Stringham, Heather M.; Swift, Amy J.; Tuomi, Tiinamaija; Uda, Manuela; Vollenweider, Peter; Waeber, Gerard; Wallace, Chris; Walters, G. Bragi; Weedon, Michael N.; Witteman, Jacqueline C. M.; Zhang, Cuilin; Zhang, Weihua; Caulfield, Mark J.; Collins, Francis S.; Davey Smith, George; Day, Ian N. M.; Franks, Paul W.; Hattersley, Andrew T.; Jarvelin, Marjo-Riitta; Kong, Augustine; Kooner, Jaspal S.; Laakso, Markku; Lakatta, Edward; Mooser, Vincent; Morris, Andrew D.; Peltonen, Leena; Samani, Nilesh J.; Spector, Timothy D.; Strachan, David P.; Tanaka, Toshiko; Tuomilehto, Jaakko; Uitterlinden, André G.; van Duijn, Cornelia M.; Wareham, Nicholas J.; Waterworth, Dawn M.; Boehnke, Michael; Deloukas, Panos; Groop, Leif; Thorsteinsdottir, Unnur; Schlessinger, David; Wichmann, H.-Erich; Frayling, Timothy M.; Abecasis, Gonçalo R.; Loos, Ruth J. F.; Stefansson, Kari; Mohlke, Karen L.; Barroso, Inês; Hirschhorn, Joel; McCarthy, Mark I.; Watkins, Hugh; The Wellcome Trust Case Control Consortium; Hunter, David; Hu, Frank; Yuan, Xin; Scott, Laura J.; Hofman, Albert; Zhao, Jing Hua; Lyon, Helen N.; Qi, LuTo identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist–hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×(10^{-11})) and MSRA (WC, P = 8.9×(10^{-9})). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×(10^{-8})). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.