A Pilot Genome-Wide Association Study in Postmenopausal Mexican-Mestizo Women Implicates the RMND1/CCDC170 Locus Is Associated with Bone Mineral Density

被引：15

作者：

Villalobos-Comparan, Marisela ^{[1
]}

Jimenez-Ortega, Rogelio F. ^{[2
]}

Estrada, Karol ^{[3
]}

Parra-Torres, Alma Y. ^{[2
]}

Gonzalez-Mercado, Anahi ^{[4
,5
]}

Patino, Nelly ^{[6
]}

Castillejos-Lopez, Manuel ^{[7
]}

Quiterio, Manuel ^{[8
]}

Carlos Fernandez-Lopez, Juan ^{[1
]}

Ibarra, Bertha ^{[4
,5
]}

Romero-Hidalgo, Sandra ^{[1
]}

Salmeron, Jorge ^{[8
,9
]}

Velazquez-Cruz, Rafael ^{[2
]}

机构：

[1] Inst Nacl Med Genom, Consorcio Genom Computac, Mexico City, DF, Mexico

[2] Inst Nacl Med Genom, Lab Genom Metab Oseo, Mexico City, DF, Mexico

[3] Biogen, Stat Genet, Cambridge, MA USA

[4] Univ Guadalajara, Ctr Univ Ciencias Salud, Guadalajara, Jalisco, Mexico

[5] IMSS, Ctr Invest Biomed Occidente, Div Genet, Guadalajara, Jalisco, Mexico

[6] Inst Nacl Med Genom, Mexico City, DF, Mexico

[7] Inst Nacl Enfermedades Resp, Unidad Vigilancia Epidemiol Hosp, Mexico City, DF, Mexico

[8] Inst Nacl Salud Publ, Ctr Invest Salud Poblac, Cuernavaca, Morelos, Mexico

[9] Inst Mexicano Seguro Social, Unidad Invest Epidemiol & Serv Salud, Cuernavaca, Morelos, Mexico

来源：

INTERNATIONAL JOURNAL OF GENOMICS | 2017年 / 2017卷

关键词：

GENE POLYMORPHISMS; OSTEOPOROSIS; METAANALYSIS; POPULATIONS; HAPLOTYPES; FRACTURES; PATTERNS; RECEPTOR; REVEALS; RISK;

D O I：

10.1155/2017/5831020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To identify genetic variants influencing bone mineral density (BMD) in the Mexican-Mestizo population, we performed a GWAS for femoral neck (FN) and lumbar spine (LS) in Mexican-Mestizo postmenopausal women. In the discovery sample, 300,000 SNPs were genotyped in a cohort of 411 postmenopausal women and seven SNPs were analyzed in the replication cohort (n = 420). The combined results of a meta-analysis from the discovery and replication samples identified two loci, RMND1 (rs6904364, P = 2 77 x 10(-4)) and CCDC170 (rs17081341, P = 1 62 x 10(-5)), associated with FN BMD. We also compared our results with those of the Genetic Factors for Osteoporosis (GEFOS) Consortium meta-analysis. The comparison revealed two loci previously reported in the GEFOS meta-analysis: SOX6 (rs7128738) and PKDCC (rs11887431) associated with FN and LS BMD, respectively, in our study population. Interestingly, rs17081341 rare in Caucasians (minor allele frequency < 0.03) was found in high frequency in our population, which suggests that this association could be specific to non-Caucasian populations. In conclusion, the first pilot Mexican GWA study of BMD confirmed previously identified loci and also demonstrated the importance of studying variability in diverse populations and/or specific populations.

引用

页数：13

共 54 条

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← 1 2 3 4 5 6 →

共 54 条

[1] A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans [J].

Acuna-Alonzo, Victor ;

Flores-Dorantes, Teresa ;

Kruit, Janine K. ;

Villarreal-Molina, Teresa ;

Arellano-Campos, Olimpia ;

Huenemeier, Tabita ;

Moreno-Estrada, Andres ;

Guadalupe Ortiz-Lopez, Ma ;

Villamil-Ramirez, Hugo ;

Leon-Mimila, Paola ;

Villalobos-Comparan, Marisela ;

Jacobo-Albavera, Leonor ;

Ramirez-Jimenez, Salvador ;

Sikora, Martin ;

Zhang, Lin-Hua ;

Pape, Terry D. ;

de Angeles Granados-Silvestre, Ma ;

Montufar-Robles, Isela ;

Tito-Alvarez, Ana M. ;

Zurita-Salinas, Camilo ;

Bustos-Arriaga, Jose ;

Cedillo-Barron, Leticia ;

Gomez-Trejo, Celta ;

Barquera-Lozano, Rodrigo ;

Vieira-Filho, Joao P. ;

Granados, Julio ;

Romero-Hidalgo, Sandra ;

Huertas-Vazquez, Adriana ;

Gonzalez-Martin, Antonio ;

Gorostiza, Amaya ;

Bonatto, Sandro L. ;

Rodriguez-Cruz, Maricela ;

Wang, Li ;

Tusie-Luna, Teresa ;

Aguilar-Salinas, Carlos A. ;

Lisker, Ruben ;

Moises, Regina S. ;

Menjivar, Marta ;

Salzano, Francisco M. ;

Knowler, William C. ;

Catira Bortolini, M. ;

Hayden, Michael R. ;

Baier, Leslie J. ;

Canizales-Quinteros, Samuel .

HUMAN MOLECULAR GENETICS, 2010, 19 (14) :2877-2885

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Adams, David ;

Altucci, Lucia ;

Antonarakis, Stylianos E. ;

Ballesteros, Juan ;

Beck, Stephan ;

Bird, Adrian ;

Bock, Christoph ;

Boehm, Bernhard ;

Campo, Elias ;

Caricasole, Andrea ;

Dahl, Fredrik ;

Dermitzakis, Emmanouil T. ;

Enver, Tariq ;

Esteller, Manel ;

Estivill, Xavier ;

Ferguson-Smith, Anne ;

Fitzgibbon, Jude ;

Flicek, Paul ;

Giehl, Claudia ;

Graf, Thomas ;

Grosveld, Frank ;

Guigo, Roderic ;

Gut, Ivo ;

Helin, Kristian ;

Jarvius, Jonas ;

Kueppers, Ralf ;

Lehrach, Hans ;

Lengauer, Thomas ;

Lernmark, Ake ;

Leslie, David ;

Loeffler, Markus ;

Macintyre, Elizabeth ;

Mai, Antonello ;

Martens, Joost H. A. ;

Minucci, Saverio ;

Ouwehand, Willem H. ;

Pelicci, Pier Giuseppe ;

Pendeville, Helene ;

Porse, Bo ;

Rakyan, Vardhman ;

Reik, Wolf ;

Schrappe, Martin ;

Schuebeler, Dirk ;

Seifert, Martin ;

Siebert, Reiner ;

Simmons, David ;

Soranzo, Nicole ;

Spicuglia, Salvatore ;

Stratton, Michael ;

Stunnenberg, Hendrik G. .

NATURE BIOTECHNOLOGY, 2012, 30 (03) :224-226

[3] Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture [J].

Alarcon-Riquelme, Marta E. ;

Ziegler, Julie T. ;

Molineros, Julio ;

Howard, Timothy D. ;

Moreno-Estrada, Andres ;

Sanchez-Rodriguez, Elena ;

Ainsworth, Hannah C. ;

Ortiz-Tello, Patricia ;

Comeau, Mary E. ;

Rasmussen, Astrid ;

Kelly, Jennifer A. ;

Adler, Adam ;

Acevedo-Vazquez, Eduardo M. ;

Cucho-Venegas, Jorge Mariano ;

Garcia-De la Torre, Ignacio ;

Cardiel, Mario H. ;

Miranda, Pedro ;

Catoggio, Luis J. ;

Maradiaga-Cecena, Marco ;

Gaffney, Patrick M. ;

Vyse, Timothy J. ;

Criswell, Lindsey A. ;

Tsao, Betty P. ;

Sivils, Kathy L. ;

Bae, Sang-Cheol ;

James, Judith A. ;

Kimberly, Robert P. ;

Kaufman, Kenneth M. ;

Harley, John B. ;

Esquivel-Valerio, Jorge A. ;

Moctezuma, Jose F. ;

Garcia, Mercedes A. ;

Berbotto, Guillermo A. ;

Babini, Alejandra M. ;

Scherbarth, Hugo ;

Toloza, Sergio ;

Baca, Vicente ;

Nath, Swapan K. ;

Salinas, Carlos Aguilar ;

Orozco, Lorena ;

Tusie-Luna, Teresa ;

Zidovetzki, Raphael ;

Pons-Estel, Bernardo A. ;

Langefeld, Carl D. ;

Jacob, Chaim O. .

ARTHRITIS & RHEUMATOLOGY, 2016, 68 (04) :932-943

[4] The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans [J].

Ardlie, Kristin G. ;

DeLuca, David S. ;

Segre, Ayellet V. ;

Sullivan, Timothy J. ;

Young, Taylor R. ;

Gelfand, Ellen T. ;

Trowbridge, Casandra A. ;

Maller, Julian B. ;

Tukiainen, Taru ;

Lek, Monkol ;

Ward, Lucas D. ;

Kheradpour, Pouya ;

Iriarte, Benjamin ;

Meng, Yan ;

Palmer, Cameron D. ;

Esko, Tonu ;

Winckler, Wendy ;

Hirschhorn, Joel N. ;

Kellis, Manolis ;

MacArthur, Daniel G. ;

Getz, Gad ;

Shabalin, Andrey A. ;

Li, Gen ;

Zhou, Yi-Hui ;

Nobel, Andrew B. ;

Rusyn, Ivan ;

Wright, Fred A. ;

Lappalainen, Tuuli ;

Ferreira, Pedro G. ;

Ongen, Halit ;

Rivas, Manuel A. ;

Battle, Alexis ;

Mostafavi, Sara ;

Monlong, Jean ;

Sammeth, Michael ;

Mele, Marta ;

Reverter, Ferran ;

Goldmann, Jakob M. ;

Koller, Daphne ;

Guigo, Roderic ;

McCarthy, Mark I. ;

Dermitzakis, Emmanouil T. ;

Gamazon, Eric R. ;

Im, Hae Kyung ;

Konkashbaev, Anuar ;

Nicolae, Dan L. ;

Cox, Nancy J. ;

Flutre, Timothee ;

Wen, Xiaoquan ;

Stephens, Matthew .

SCIENCE, 2015, 348 (6235) :648-660

[5] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[6] Disease variants alter transcription factor levels and methylation of their binding sites [J].

Bonder, Marc Jan ;

Luijk, Rene ;

Zhernakova, Dania V. ;

Moed, Matthijs ;

Deelen, Patrick ;

Vermaat, Martijn ;

van Iterson, Maarten ;

van Dijk, Freerk ;

van Galen, Michiel ;

Bot, Jan ;

Slieker, Roderick C. ;

Jhamai, P. Mila ;

Verbiest, Michael ;

Suchiman, H. Eka D. ;

Verkerk, Marijn ;

van der Breggen, Ruud ;

van Rooij, Jeroen ;

Lakenberg, Nico ;

Arindrarto, Wibowo ;

Kielbasa, Szymon M. ;

Jonkers, Iris ;

van 't Hof, Peter ;

Nooren, Irene ;

Beekman, Marian ;

Deelen, Joris ;

van Heemst, Diana ;

Zhernakova, Alexandra ;

Tigchelaar, Ettje F. ;

Swertz, Morris A. ;

Hofman, Albert ;

Uitterlinden, Andre G. ;

Pool, Rene ;

van Dongen, Jenny ;

Hottenga, Jouke J. ;

Stehouwer, Coen D. A. ;

van der Kallen, Carla J. H. ;

Schalkwijk, Casper G. ;

van den Berg, Leonard H. ;

van Zwet, Erik W. ;

Mei, Hailiang ;

Li, Yang ;

Lemire, Mathieu ;

Hudson, Thomas J. ;

Slagboom, P. Eline ;

Wijmenga, Cisca ;

Veldink, Jan H. ;

van Greevenbroek, Marleen M. J. ;

van Duijn, Cornelia M. ;

Boomsma, Dorret I. ;

Isaacs, Aaron .

NATURE GENETICS, 2017, 49 (01) :131-138

[7] HISTONE DEACETYLASES IN BONE DEVELOPMENT AND SKELETAL DISORDERS [J].

Bradley, Elizabeth W. ;

Carpio, Lomeli R. ;

van Wijnen, Andre J. ;

McGee-Lawrence, Meghan E. ;

Westendorf, Jennifer J. .

PHYSIOLOGICAL REVIEWS, 2015, 95 (04) :1359-1381

[8] Health care costs of osteopenia, osteoporosis, and fragility fractures in Mexico [J].

Carlos, Fernando ;

Clark, Patricia ;

Maria Galindo-Suarez, Rosa ;

Gabriela Chico-Barba, Laura .

ARCHIVES OF OSTEOPOROSIS, 2013, 8 (1-2)

[9] A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits [J].

Cho, Yoon Shin ;

Go, Min Jin ;

Kim, Young Jin ;

Heo, Jee Yeon ;

Oh, Ji Hee ;

Ban, Hyo-Jeong ;

Yoon, Dankyu ;

Lee, Mi Hee ;

Kim, Dong-Joon ;

Park, Miey ;

Cha, Seung-Hun ;

Kim, Jun-Woo ;

Han, Bok-Ghee ;

Min, Haesook ;

Ahn, Younjhin ;

Park, Man Suk ;

Han, Hye Ree ;

Jang, Hye-Yoon ;

Cho, Eun Young ;

Lee, Jong-Eun ;

Cho, Nam H. ;

Shin, Chol ;

Park, Taesung ;

Park, Ji Wan ;

Lee, Jong-Keuk ;

Cardon, Lon ;

Clarke, Geraldine ;

McCarthy, Mark I. ;

Lee, Jong-Young ;

Lee, Jong-Koo ;

Oh, Bermseok ;

Kim, Hyung-Lae .

NATURE GENETICS, 2009, 41 (05) :527-534

[10] Genome-wide association study in East Asians suggests UHMK1 as a novel bone mineral density susceptibility gene [J].

Choi, Hyung Jin ;

Park, Hyojung ;

Zhang, Lei ;

Kim, Jung Hee ;

Kim, Ye An ;

Yang, Jae-Yeon ;

Pei, Yu-Fang ;

Tian, Qing ;

Shen, Hui ;

Hwang, Joo-Yeon ;

Deng, Hong-Wen ;

Cho, Nam H. ;

Chan, Soo Shin .

BONE, 2016, 91 :113-121

← 1 2 3 4 5 6 →