Search

Your search keyword '"Denise Houston"' showing total 6 results
Start Over Author "Denise Houston"
6 results on '"Denise Houston"'

1. A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: results from the Population Architecture using Genomics and Epidemiology (PAGE) study.

Author

Ulrike Peters, Kari E North, Praveen Sethupathy, Steve Buyske, Jeff Haessler, Shuo Jiao, Megan D Fesinmeyer, Rebecca D Jackson, Lew H Kuller, Aleksandar Rajkovic, Unhee Lim, Iona Cheng, Fred Schumacher, Lynne Wilkens, Rongling Li, Keri Monda, Georg Ehret, Khanh-Dung H Nguyen, Richard Cooper, Cora E Lewis, Mark Leppert, Marguerite R Irvin, C Charles Gu, Denise Houston, Petra Buzkova, Marylyn Ritchie, Tara C Matise, Loic Le Marchand, Lucia A Hindorff, Dana C Crawford, Christopher A Haiman, and Charles Kooperberg

Subjects
Genetics, QH426-470
Abstract

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3 × 10(-6)) had not been highlighted in previous studies. While rs56137030was correlated at r(2)>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations.

Published
2013
Full Text
View/download PDF

2. Weight Change During the Postintervention Follow-up of Look AHEAD

Author

Rena R. Wing, Rebecca H. Neiberg, Judy L. Bahnson, Jeanne M. Clark, Mark A. Espeland, James O. Hill, Karen C. Johnson, William C. Knowler, KayLoni Olson, Helmut Steinburg, Xavier Pi-Sunyer, Thomas A. Wadden, Holly Wyatt, Lee Swartz, Dawn Jiggetts, Jeanne Charleston, Lawrence Cheskin, Nisa M. Maruthur, Scott J. Pilla, Danielle Diggins, Mia Johnson, George A. Bray, Frank L. Greenway, Donna H. Ryan, Catherine Champagne, Valerie Myers, Jeffrey Keller, Tiffany Stewart, Jennifer Arceneaux, Karen Boley, Greta Fry, Lisa Jones, Kim Landry, Melissa Lingle, Marisa Smith, Cora E. Lewis, Sheikilya Thomas, Stephen Glasser, Gareth Dutton, Amy Dobelstein, Sara Hannum, Anne Hubbell, DeLavallade Lee, Phyllis Millhouse, L. Christie Oden, Cathy Roche, Jackie Grant, Janet Turman, David M. Nathan, Valerie Goldman, Linda Delahanty, Mary Larkin, Kristen Dalton, Roshni Singh, Melanie Ruazol, Medha N. Munshi, Sharon D. Jackson, Roeland J.W. Middelbeek, A. Enrique Caballero, Anthony Rodriguez, George Blackburn, Christos Mantzoros, Ann McNamara, Jeanne Anne Breen, Marsha Miller, Debbie Bochert, Suzette Bossart, Paulette Cohrs, Susan Green, April Hamilton, Eugene Leshchinskiy, Loretta Rome, John P. Foreyt, Molly Gee, Henry Pownall, Ashok Balasubramanyam, Chu-Huang Chen, Peter Jones, Michele Burrington, Allyson Clark Gardner, Sharon Griggs, Michelle Hamilton, Veronica Holley, Sarah Lee, Sarah Lane Liscum, Susan Cantu-Lumbreras, Julieta Palencia, Jennifer Schmidt, Jayne Thomas, Carolyn White, Charlyne Wright, Monica Alvarez, Beate Griffin, Mace Coday, Donna Valenski, Karen Johnson, Robert W. Jeffery, Tricia Skarphol, John P. Bantle, J. Bruce Redmon, Kerrin Brelje, Carolyne Campbell, Mary Ann Forseth, Soni Uccellini, Mary Susan Voeller, Blandine Laferrère, Jennifer Patricio, Jose Luchsinger, Priya Palta, Sarah Lyon, Kim Kelly, Barbara J. Maschak-Carey, Robert I. Berkowitz, Ariana Chao, Renee Davenport, Katherine Gruber, Sharon Leonard, Olivia Walsh, John M. Jakicic, Jacqueline Wesche-Thobaben, Lin Ewing, Andrea Hergenroeder, Mary Korytkowski, Susan Copelli, Rebecca Danchenko, Diane Ives, Juliet Mancino, Lisa Martich, Meghan McGuire, Tracey Y. Murray, Linda Semler, Kathy Williams, Caitlin Egan, Elissa Jelalian, Jeanne McCaffery, Kathryn Demos McDermott, Jessica Unick, Kirsten Annis, Jose DaCruz, Ariana Rafanelli, Helen P. Hazuda, Juan Carlos Isaac, Prepedigna Hernandez, Steven E. Kahn, Edward J. Boyko, Elaine Tsai, Lorena Wright, Karen Atkinson, Ivy Morgan-Taggart, Jolanta Socha, Heidi Urquhart, Paula Bolin, Harelda Anderson, Sara Michaels, Ruby Johnson, Patricia Poorthunder, Janelia Smiley, Anne L. Peters, Siran Ghazarian, Elizabeth Beale, Edgar Ramirez, Gabriela Rodriguez, Valerie Ruelas, Sara Serafin-Dokhan, Martha Walker, Marina Perez, Lynne E. Wagenknecht, David Reboussin, Mike E. Miller, Peter Brubaker, Nicholas Pajewski, Michael Bancks, Jingzhong Ding, Gagan Deep, Kathleen Hayden, Stephen R. Rapp, Felicia Simpson, Haiying Chen, Bonnie C. Sachs, Denise Houston, Shyh-Huei Chen, Andrea Anderson, Jerry M. Barnes, Mary Barr, Tara D. Beckner, Delilah R. Cook, Carrie C. Williams, Joni Evans, Katie Garcia, Sarah A. Gaussoin, Carol Kittel, Lea Harvin, Marjorie Howard, James Lovato, June Pierce, Debbie Steinberg, Christopher Webb, Jennifer Walker, Michael P. Walkup, Carolyn Watkins, Santica M. Marcovina, Jessica Hurting, John J. Albers, Vinod Gaur, Michael Nevitt, Ann Schwartz, John Shepherd, Michaela Rahorst, Lisa Palermo, Susan Ewing, Cynthia Hayashi, and Jason Maeda

Subjects
Advanced and Specialized Nursing, Endocrinology, Diabetes and Metabolism, Internal Medicine, Clinical Care/Education/Nutrition/Psychosocial Research
Abstract

OBJECTIVE Patients with type 2 diabetes are encouraged to lose weight, but excessive weight loss in older adults may be a marker of poor health and subsequent mortality. We examined weight change during the postintervention period of Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) with diabetes support and education (DSE) (control) in overweight/obese individuals with type 2 diabetes and sought to identify predictors of excessive postintervention weight loss and its association with mortality. RESEARCH DESIGN AND METHODS These secondary analyses compared postintervention weight change (year 8 to final visit; median 16 years) in ILI and DSE in 3,999 Look AHEAD participants. Using empirically derived trajectory categories, we compared four subgroups: weight gainers (n = 307), weight stable (n = 1,561), steady losers (n = 1,731), and steep losers (n = 380), on postintervention mortality, demographic variables, and health status at randomization and year 8. RESULTS Postintervention weight change averaged −3.7 ± 9.5%, with greater weight loss in the DSE than the ILI group. The steep weight loss trajectory subgroup lost on average 17.7 ± 6.6%; 30% of steep losers died during postintervention follow-up versus 10–18% in other trajectories (P < 0001). The following variables distinguished steep losers from weight stable: baseline, older, longer diabetes duration, higher BMI, and greater multimorbidity; intervention, randomization to control group and less weight loss in years 1–8; and year 8, higher prevalence of frailty, multimorbidity, and depressive symptoms and lower use of weight control strategies. CONCLUSIONS Steep weight loss postintervention was associated with increased risk of mortality. Older individuals with longer duration of diabetes and multimorbidity should be monitored for excessive unintentional weight loss.

Published
2021

4. In Reply

Author

Candace Y. Parker-Autry, Denise Houston, Stephen Kritchevsky, and Holly E. Richter

Subjects
Urinary Incontinence, Obstetrics and Gynecology, Humans, Female, Aged
Published
2018

5. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts

Author

Benjamin Voight, Guillaume Pare, Ruth Loos, Michael Preuss, Åsa Johansson, Eco De Geus, Michael Weedon, Marjo-Riitta Jarvelin, Joyce Van Meurs, Torben Jørgensen, Kirsi Pietiläinen, Nicole Glazer, Mattias Lorentzon, Braxton Mitchell, Nicole Soranzo, Patricia Munroe, Ozren Polasek, Elisabeth Thiering, Marika Kaakinen, Carla Vogel, Jennie Hui, Elina Hypponen, ROBERTO ELOSUA, Amanda Bennett, Michael Stumvoll, Andrew Hattersley, Peter P Pramstaller, Lambertus Kiemeney, Sophie Visvikis-Siest, Vilmundur Gudnason, John Whittaker, Aroon Hingorani, Thor Aspelund, Dale Nyholt, Mary Feitosa, Vimal Karani, Mika Kähönen, Lachlan Coin, Malcolm Dunlop, Josee Dupuis, Terho Lehtimäki, Peter Visscher, Katja Aben, Daniel Witte, Cyrus Cooper, Stefan Pilz, Willem Ouwehand, Eleanor Wheeler, Peter Kovacs, Debbie A Lawlor, Kevin Jacobs, Evropi Theodoratou, Hana Lango Allen, Rosanda Mulic, Rui Li, Stephen Kritchevsky, Philippe Froguel, Soumya Raychaudhuri, Cornelia Van Duijn, Andrew Wood, Chiara Lanzani, Tonu Esko, Sadaf Farooqi, Reedik Mägi, Gerard Waeber, Claes Ohlsson, André Scherag, Marcus Kleber, Thomas Meitinger, Lina Zgaga, Denise Houston, Karl Michaëlsson, Robert Weyant, Thomas Wang, Paul Elliott, Robert Luben, Albert Vernon Smith, MANUELA UDA, Gonneke Willemsen, Mark McCarthy, Cecilia Lindgren, Olle Melander, Igor Rudan, Maris Teder-Laving, Liesbeth Vandenput, Vimaleswaran, K, Berry, Dj, Lu, C, Tikkanen, E, Pilz, S, Hiraki, Lt, Cooper, Jd, Dastani, Z, Li, R, Houston, Dk, Wood, Ar, Michaëlsson, K, Vandenput, L, Zgaga, L, YERGES ARMSTRONG, Lm, Mccarthy, Mi, Dupuis, J, Kaakinen, M, Kleber, Me, Jameson, K, Arden, N, Raitakari, O, Viikari, J, Lohman, Kk, Ferrucci, L, Melhus, H, Ingelsson, E, Byberg, L, Lind, L, Lorentzon, M, Salomaa, V, Campbell, H, Dunlop, M, Mitchell, Bd, Herzig, Kh, Pouta, A, Hartikainen, Al, Manunta, Paolo, Streeten, Ea, Theodoratou, E, Jula, A, Wareham, Nj, Ohlsson, C, Frayling, Tm, Kritchevsky, Sb, Spector, Td, Richards, Jb, Lehtimäki, T, Ouwehand, Wh, Kraft, P, Cooper, C, März, W, Power, C, Loos, Rj, Wang, Tj, Järvelin, Mr, Whittaker, Jc, Hingorani, Ad, Hyppönen, E., Council, Medical Research, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Institute for Molecular Medicine Finland, Haartman Institute (-2014), Transplantation Laboratory, Vimaleswaran, Karani S, Berry, Diane J, Lu, Chen, Tikkanen, Emmi, Hyppönen, Elina, Genetic Investigation of Anthropometric Traits (GIANT) Consortium, Hinney, Anke (Beitragende*r), Scherag, Susann (Beitragende*r), Hebebrand, Johannes (Beitragende*r), Epidemiology and Data Science, Psychiatry, EMGO - Lifestyle, overweight and diabetes, Genetic Investigation of Anthropometric Traits-GIANT Consortium, Speliotes, E.K., Willer, C.J., Berndt, S.I., Monda, K.L., Thorleifsson, G., Jackson, A.U., Allen, H.L., Lindgren, C.M., Jian'an, L., Mägi, R., Randall, J.C., Vedantam, S., Winkler, T.W., Qi, L., Workalemahu, T., Heid, I.M., Steinthorsdottir, V., Stringham, H.M., Weedon, M.N., Wheeler, E., Wood, A.R., Ferreira, T., Weyant, R.J., Segrè, A.V., Estrada, K., Liang, L., Nemesh, J., Park, J.H., Gustafsson, S., Kilpeläinen, T.O., Yang, J., Bouatia-Naji, N., Tõnu, E., Feitosa, M.F., Kutalik, Z., Mangino, M., Raychaudhuri, S., Scherag, A., Smith, A.V., Welch, R., Zhao, J.H., Aben, K.K., Absher, D.M., Amin, N., Dixon, A.L., Fisher, E., Glazer, N.L., Goddard, M.E., Heard-Costa, N.L., Hoesel, V., Hottenga, J.J., Johansson, Å., Johnson, T., Ketkar, S., Lamina, C., Li, S., Moffatt, M.F., Myers, R.H., Narisu, N., Perry, J.R., Peters, M.J., Preuss, M., Ripatti, S., Rivadeneira, F., Sandholt, C., Scott, L.J., Timpson, N.J., Tyrer, J.P., van Wingerden, S., Watanabe, R.M., White, C.C., Wiklund, F., Barlassina, C., Chasman, D.I., Cooper, M.N., Jansson, J.O., Lawrence, R.W., Pellikka, N., Prokopenko, I., Shi, J., Thiering, E., Alavere, H., Alibrandi, M.T., Almgren, P., Arnold, A.M., Aspelund, T., Atwood, L.D., Balkau, B., Balmforth, A.J., Bennett, A.J., Ben-Shlomo, Y., Bergman, R.N., Bergmann, S., Biebermann, H., Blakemore, A.I., Boes, T., Bonnycastle, L.L., Bornstein, S.R., Brown, M.J., Buchanan, T.A., Busonero, F., Campbell, H., Cappuccio, F.P., Cavalcanti-Proença, C., Chen, Y.D., Chen, C.M., Chines, P.S., Clarke, R., Coin, L., Connell, J., Day, I.N., Heijer, M., Duan, J., Ebrahim, S., Elliott, P., Elosua, R., Eiriksdottir, G., Erdos, M.R., Eriksson, J.G., Facheris, M.F., Felix, S.B., Fischer-Posovszky, P., Folsom, A.R., Friedrich, N., Freimer, N.B., Fu, M., Gaget, S., Gejman, P.V., Geus, E.J., Gieger, C., Gjesing, A.P., Goel, A., Goyette, P., Grallert, H., Gräßler, J., Greenawalt, D.M., Groves, C.J., Gudnason, V., Guiducci, C., Hartikainen, A.L., Hassanali, N., Hall, A.S., Havulinna, A.S., Hayward, C., Heath, A.C., Hengstenberg, C., Hicks, A.A., Hinney, A., Hofman, A., Homuth, G., Hui, J., Igl, W., Iribarren, C., Isomaa, B., Jacobs, K.B., Jarick, I., Jewell, E., John, U., Jørgensen, T., Jousilahti, P., Jula, A., Kaakinen, M., Kajantie, E., Kaplan, L.M., Kathiresan, S., Kettunen, J., Kinnunen, L., Knowles, J.W., Kolcic, I., König, I.R., Koskinen, S., Kovacs, P., Kuusisto, J., Kraft, P., Kvaløy, K., Laitinen, J., Lantieri, O., Lanzani, C., Launer, L.J., Lecoeur, C., Lehtimäki, T., Lettre, G., Liu, J., Lokki, M.L., Lorentzon, M., Luben, R.N., Ludwig, B., Manunta, P., Marek, D., Marre, M., Martin, N.G., McArdle, W.L., McCarthy, A., McKnight, B., Meitinger, T., Melander, O., Meyre, D., Midthjell, K., Montgomery, G.W., Morken, M.A., Morris, A.P., Mulic, R., Ngwa, J.S., Nelis, M., Neville, M.J., Nyholt, D.R., O'Donnell, C.J., O'Rahilly, S., Ong, K.K., Oostra, B., Paré, G., Parker, A.N., Perola, M., Pichler, I., Pietiläinen, K.H., Platou, C.G., Polasek, O., Pouta, A., Rafelt, S., Raitakari, O., Rayner, N.W., Ridderstråle, M., Rief, W., Ruokonen, A., Robertson, N.R., Rzehak, P., Salomaa, V., Sanders, A.R., Sandhu, M.S., Sanna, S., Saramies, J., Savolainen, M.J., Scherag, S., Schipf, S., Schreiber, S., Schunkert, H., Silander, K., Sinisalo, J., Siscovick, D.S., Smit, J.H., Soranzo, N., Sovio, U., Stephens, J., Surakka, I., Swift, AJ., Tammesoo, M.L., Tardif, J.C., Teder-Laving, M., Teslovich, T.M., Thompson, J.R., Thomson, B., Tönjes, A., Tuomi, T., van Meurs, J.B., van Ommen, G.J., Vatin, V., Viikari, J., Visvikis-Siest, S., Vitart, V., Vogel, C.I., Voight, B.F., Waite, L.L., Wallaschofski, H., Walters, G.B., Widen, E., Wiegand, S., Wild, S.H., Willemsen, G., Witte, D.R., Witteman, J.C., Xu, J., Zhang, Q., Zgaga, L., Ziegler, A., Zitting, P., Beilby, J.P., Farooqi, I.S., Hebebrand, J., Huikuri, H.V., James, AL., Kähönen, M., Levinson, D.F., Macciardi, F., Nieminen, M.S., Ohlsson, C., Palmer, L.J., Ridker, P.M., Stumvoll, M., Beckmann, J.S., Boeing, H., Boerwinkle, E., Boomsma, D.I., Caulfield, M.J., Chanock, S.J., Collins, F.S., Cupples, L.A., Smith, G.D., Erdmann, J., Froguel, P., Grönberg, H., Gyllensten, U., Hall, P., Hansen, T., Harris, T.B., Hattersley, A.T., Hayes, R.B., Heinrich, J., Hu, F.B., Hveem, K., Illig, T., Jarvelin, M.R., Kaprio, J., Karpe, F., Khaw, K.T., Kiemeney, L.A., Krude, H., Laakso, M., Lawlor, D.A., Metspalu, A., Munroe, P.B., Ouwehand, W.H., Pedersen, O., Penninx, B.W., Peters, A., Pramstaller, P.P., Quertermous, T., Reinehr, T., Rissanen, A., Rudan, I., Samani, N.J., Schwarz, P.E., Shuldiner, A.R., Spector, T.D., Tuomilehto, J., Uda, M., Uitterlinden, A., Valle, T.T., Wabitsch, M., Waeber, G., Wareham, N.J., Watkins, H., Wilson, J.F., Wright, A.F., Zillikens, M.C., Chatterjee, N., McCarroll, S.A., Purcell, S., Schadt, E.E., Visscher, P.M., Assimes, T.L., Borecki, I.B., Deloukas, P., Fox, C.S., Groop, L.C., Haritunians, T., Hunter, D.J., Kaplan, R.C., Mohlke, K.L., O'Connell, J.R., Peltonen, L., Schlessinger, D., Strachan, D.P., van Duijn, C.M., Wichmann, H.E., Frayling, T.M., Thorsteinsdottir, U., Abecasis, G.R., Barroso, I., Boehnke, M., Stefansson, K., North, K.E., McCarthy, M.I., Hirschhorn, J.N., Ingelsson, E., Loos, R.J., Medical Research Council (MRC), and National Institute for Health Research

Subjects
Male, Netherlands Twin Register (NTR), Medicin och hälsovetenskap, obesity, 25-HYDROXYVITAMIN D, D INSUFFICIENCY, Epidemiology, Medizin, vitamin D, Aetiology, screening and detection [ONCOL 5], Medical and Health Sciences, Gastroenterology, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, GENETIC-VARIANTS, Medicine, 030212 general & internal medicine, Vitamin D, 2. Zero hunger, Genetics, Aged, 80 and over, Evidence-Based Medicine, Confounding, 11 Medical And Health Sciences, General Medicine, Middle Aged, 3. Good health, PREVALENCE, Europe, Phenotype, Genetic Epidemiology, Biological Markers, Female, Life Sciences & Biomedicine, Research Article, Vitamin, Adult, medicine.medical_specialty, vitamin D deficiency, genetic variants, Genetic Investigation of Anthropometric Traits-GIANT Consortium, European Continental Ancestry Group, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, body mass index, Polymorphism, Single Nucleotide, Risk Assessment, White People, COMMON OBESITY, 03 medical and health sciences, D DEFICIENCY, Medicine, General & Internal, SDG 3 - Good Health and Well-being, General & Internal Medicine, Internal medicine, Mendelian randomization, Vitamin D and neurology, INSTRUMENTAL VARIABLES, Humans, Genetic Predisposition to Disease, Obesity, GENOME-WIDE ASSOCIATION, Biology, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], Aged, Science & Technology, Population Biology, business.industry, CARDIOVASCULAR-DISEASE RISK, ta3121, Mendelian Randomization Analysis, medicine.disease, Vitamin D Deficiency, BODY-MASS INDEX, chemistry, Genetic epidemiology, 3121 General medicine, internal medicine and other clinical medicine, Multivariate Analysis, North America, Genetic Polymorphism, Linear Models, business, Body mass index, Population Genetics, Biomarkers
Abstract

A mendelian randomization study based on data from multiple cohorts conducted by Karani Santhanakrishnan Vimaleswaran and colleagues re-examines the causal nature of the relationship between vitamin D levels and obesity., Background Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and Findings We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m2 higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10−27). The BMI allele score was associated both with BMI (p = 6.30×10−62) and 25(OH)D (−0.06% [95% CI −0.10 to −0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10−57 for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: −4.2 [95% CI −7.1 to −1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). Conclusions On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency. Please see later in the article for the Editors' Summary, Editors' Summary Background Obesity—having an unhealthy amount of body fat—is increasing worldwide. In the US, for example, a third of the adult population is now obese. Obesity is defined as having a body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) of more than 30.0 kg/m2. Although there is a genetic contribution to obesity, people generally become obese by consuming food and drink that contains more energy than they need for their daily activities. Thus, obesity can be prevented by having a healthy diet and exercising regularly. Compared to people with a healthy weight, obese individuals have an increased risk of developing diabetes, heart disease and stroke, and tend to die younger. They also have a higher risk of vitamin D deficiency, another increasingly common public health concern. Vitamin D, which is essential for healthy bones as well as other functions, is made in the skin after exposure to sunlight but can also be obtained through the diet and through supplements. Why Was This Study Done? Observational studies cannot prove that obesity causes vitamin D deficiency because obese individuals may share other characteristics that reduce their circulating 25-hydroxy vitamin D [25(OH)D] levels (referred to as confounding). Moreover, observational studies cannot indicate whether the larger vitamin D storage capacity of obese individuals (vitamin D is stored in fatty tissues) lowers their 25(OH)D levels or whether 25(OH)D levels influence fat accumulation (reverse causation). If obesity causes vitamin D deficiency, monitoring and treating vitamin D deficiency might alleviate some of the adverse health effects of obesity. Conversely, if low vitamin D levels cause obesity, encouraging people to take vitamin D supplements might help to control the obesity epidemic. Here, the researchers use bi-directional “Mendelian randomization” to examine the direction and causality of the relationship between BMI and 25(OH)D. In Mendelian randomization, causality is inferred from associations between genetic variants that mimic the influence of a modifiable environmental exposure and the outcome of interest. Because gene variants do not change over time and are inherited randomly, they are not prone to confounding and are free from reverse causation. Thus, if a lower vitamin D status leads to obesity, genetic variants associated with lower 25(OH)D concentrations should be associated with higher BMI, and if obesity leads to a lower vitamin D status, then genetic variants associated with higher BMI should be associated with lower 25(OH)D concentrations. What Did the Researchers Do and Find? The researchers created a “BMI allele score” based on 12 BMI-related gene variants and two “25(OH)D allele scores,” which are based on gene variants that affect either 25(OH)D synthesis or breakdown. Using information on up to 42,024 participants from 21 studies, the researchers showed that the BMI allele score was associated with both BMI and with 25(OH)D levels among the study participants. Based on this information, they calculated that each 10% increase in BMI will lead to a 4.2% decrease in 25(OH)D concentrations. By contrast, although both 25(OH)D allele scores were strongly associated with 25(OH)D levels, neither score was associated with BMI. This lack of an association between 25(OH)D allele scores and obesity was confirmed using data from more than 100,000 individuals involved in 46 studies that has been collected by the GIANT (Genetic Investigation of Anthropometric Traits) consortium. What Do These Findings Mean? These findings suggest that a higher BMI leads to a lower vitamin D status whereas any effects of low vitamin D status on BMI are likely to be small. That is, these findings provide evidence for obesity as a causal factor in the development of vitamin D deficiency but not for vitamin D deficiency as a causal factor in the development of obesity. These findings suggest that population-level interventions to reduce obesity should lead to a reduction in the prevalence of vitamin D deficiency and highlight the importance of monitoring and treating vitamin D deficiency as a means of alleviating the adverse influences of obesity on health. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001383. The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (in English and Spanish); a data brief provides information about the vitamin D status of the US population The World Health Organization provides information on obesity (in several languages) The UK National Health Service Choices website provides detailed information about obesity and a link to a personal story about losing weight; it also provides information about vitamin D The International Obesity Taskforce provides information about the global obesity epidemic The US Department of Agriculture's ChooseMyPlate.gov website provides a personal healthy eating plan; the Weight-control Information Network is an information service provided for the general public and health professionals by the US National Institute of Diabetes and Digestive and Kidney Diseases (in English and Spanish) The US Office of Dietary Supplements provides information about vitamin D (in English and Spanish) MedlinePlus has links to further information about obesity and about vitamin D (in English and Spanish) Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) Overview and details of the collaborative large-scale genetic association study (D-CarDia) provide information about vitamin D and the risk of cardiovascular disease, diabetes and related traits

Published
2013
Full Text
View/download PDF

6. Dietary fiber intake and glycemic index and incidence of diabetes in African-American and white adults: the ARIC study

Author

June, Stevens, Kyungmi, Ahn, Juhaeri, Denise, Houston, Lyn, Steffan, and David, Couper

Subjects
Adult, Blood Glucose, Dietary Fiber, Arteriosclerosis, Risk Factors, Incidence, Surveys and Questionnaires, Diabetes Mellitus, North Carolina, Black People, Humans, Energy Intake, White People
Abstract

To determine the association of dietary fiber and glycemic index with incident type 2 diabetes in African-Americans and whites.We studied 12,251 adults aged 45-64 years and free of diabetes at baseline (1987-1989). A total of 1,447 cases of diabetes were reported between baseline and 9 years of follow-up. Diabetes status was determined by fasting glucose levelor =126 mg/dl (7.0 mmol/l), nonfasting glucose levelor =200 mg/dl (11.1 mmol/l), self-report of physician diagnosis, or use of diabetes medication. Usual dietary intake over the previous year was obtained at baseline using a 66-item food-frequency questionnaire. Nutrients were energy-adjusted using the residuals method. Proportional hazard regression analysis was used to examine dietary fiber intake and glycemic index as predictors of type 2 diabetes in both ethnic groups.After adjustment for age, BMI, education, smoking status, physical activity, sex, and field center, there were no statistically significant associations of intake of total dietary fiber, fruit fiber, legume fiber, glycemic index, or glycemic load with incident diabetes. The hazard ratio for the fifth compared with the first quintile of cereal fiber was 0.75 (95% CI 0.60-0.92) in whites and 0.86 (0.65-1.15) in African-Americans.This finding supports a protective role for cereal fiber in the development of diabetes in whites. More studies are needed to determine the role of dietary fiber and glycemic index in diabetes in African-Americans.

Published
2002

Catalog

Books, media, physical & digital resources
See catalog results