@article {1556,
	title = {Assessment of gene-by-sex interaction effect on bone mineral density.},
	journal = {J Bone Miner Res},
	volume = {27},
	year = {2012},
	month = {2012 Oct},
	pages = {2051-64},
	abstract = {<p>Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 {\texttimes} 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 {\texttimes} 10(-5) ; female effect = -0.007 and p = 3.3 {\texttimes} 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 {\texttimes} 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08\% of the variation in these traits per implicated SNP. {\textcopyright} 2012 American Society for Bone and Mineral Research.</p>},
	keywords = {Bone Density, Cohort Studies, Female, Genes, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results, Sex Characteristics},
	issn = {1523-4681},
	doi = {10.1002/jbmr.1679},
	author = {Liu, Ching-Ti and Estrada, Karol and Yerges-Armstrong, Laura M and Amin, Najaf and Evangelou, Evangelos and Li, Guo and Minster, Ryan L and Carless, Melanie A and Kammerer, Candace M and Oei, Ling and Zhou, Yanhua and Alonso, Nerea and Dailiana, Zoe and Eriksson, Joel and Garc{\'\i}a-Giralt, Natalia and Giroux, Sylvie and Husted, Lise Bjerre and Khusainova, Rita I and Koromila, Theodora and Kung, Annie Waichee and Lewis, Joshua R and Masi, Laura and Mencej-Bedrac, Simona and Nogues, Xavier and Patel, Millan S and Prezelj, Janez and Richards, J Brent and Sham, Pak Chung and Spector, Timothy and Vandenput, Liesbeth and Xiao, Su-Mei and Zheng, Hou-Feng and Zhu, Kun and Balcells, Susana and Brandi, Maria Luisa and Frost, Morten and Goltzman, David and Gonz{\'a}lez-Mac{\'\i}as, Jes{\'u}s and Karlsson, Magnus and Khusnutdinova, Elza K and Kollia, Panagoula and Langdahl, Bente Lomholt and Ljunggren, Osten and Lorentzon, Mattias and Marc, Janja and Mellstr{\"o}m, Dan and Ohlsson, Claes and Olmos, Jos{\'e} M and Ralston, Stuart H and Riancho, Jos{\'e} A and Rousseau, Fran{\c c}ois and Urreizti, Roser and Van Hul, Wim and Zarrabeitia, Mar{\'\i}a T and Castano-Betancourt, Martha and Demissie, Serkalem and Grundberg, Elin and Herrera, Lizbeth and Kwan, Tony and Medina-G{\'o}mez, Carolina and Pastinen, Tomi and Sigurdsson, Gunnar and Thorleifsson, Gudmar and Vanmeurs, Joyce Bj and Blangero, John and Hofman, Albert and Liu, Yongmei and Mitchell, Braxton D and O{\textquoteright}Connell, Jeffrey R and Oostra, Ben A and Rotter, Jerome I and Stefansson, Kari and Streeten, Elizabeth A and Styrkarsdottir, Unnur and Thorsteinsdottir, Unnur and Tylavsky, Frances A and Uitterlinden, Andre and Cauley, Jane A and Harris, Tamara B and Ioannidis, John Pa and Psaty, Bruce M and Robbins, John A and Zillikens, M Carola and Vanduijn, Cornelia M and Prince, Richard L and Karasik, David and Rivadeneira, Fernando and Kiel, Douglas P and Cupples, L Adrienne and Hsu, Yi-Hsiang}
}
@article {8016,
	title = {Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.},
	journal = {Nat Genet},
	volume = {44},
	year = {2012},
	month = {2012 Apr 15},
	pages = {491-501},
	abstract = {<p>Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 {\texttimes} 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 {\texttimes} 10(-4), Bonferroni corrected), of which six reached P < 5 {\texttimes} 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.</p>},
	keywords = {Bone Density, Computational Biology, European Continental Ancestry Group, Extracellular Matrix Proteins, Female, Femur Neck, Fractures, Bone, Gene Expression Profiling, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Glycoproteins, Humans, Intercellular Signaling Peptides and Proteins, Low Density Lipoprotein Receptor-Related Protein-5, Lumbar Vertebrae, Male, Mitochondrial Membrane Transport Proteins, Osteoporosis, Phosphoproteins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors, Spectrin},
	issn = {1546-1718},
	doi = {10.1038/ng.2249},
	author = {Estrada, Karol and Styrkarsdottir, Unnur and Evangelou, Evangelos and Hsu, Yi-Hsiang and Duncan, Emma L and Ntzani, Evangelia E and Oei, Ling and Albagha, Omar M E and Amin, Najaf and Kemp, John P and Koller, Daniel L and Li, Guo and Liu, Ching-Ti and Minster, Ryan L and Moayyeri, Alireza and Vandenput, Liesbeth and Willner, Dana and Xiao, Su-Mei and Yerges-Armstrong, Laura M and Zheng, Hou-Feng and Alonso, Nerea and Eriksson, Joel and Kammerer, Candace M and Kaptoge, Stephen K and Leo, Paul J and Thorleifsson, Gudmar and Wilson, Scott G and Wilson, James F and Aalto, Ville and Alen, Markku and Aragaki, Aaron K and Aspelund, Thor and Center, Jacqueline R and Dailiana, Zoe and Duggan, David J and Garcia, Melissa and Garc{\'\i}a-Giralt, Natalia and Giroux, Sylvie and Hallmans, G{\"o}ran and Hocking, Lynne J and Husted, Lise Bjerre and Jameson, Karen A and Khusainova, Rita and Kim, Ghi Su and Kooperberg, Charles and Koromila, Theodora and Kruk, Marcin and Laaksonen, Marika and LaCroix, Andrea Z and Lee, Seung Hun and Leung, Ping C and Lewis, Joshua R and Masi, Laura and Mencej-Bedrac, Simona and Nguyen, Tuan V and Nogues, Xavier and Patel, Millan S and Prezelj, Janez and Rose, Lynda M and Scollen, Serena and Siggeirsdottir, Kristin and Smith, Albert V and Svensson, Olle and Trompet, Stella and Trummer, Olivia and van Schoor, Natasja M and Woo, Jean and Zhu, Kun and Balcells, Susana and Brandi, Maria Luisa and Buckley, Brendan M and Cheng, Sulin and Christiansen, Claus and Cooper, Cyrus and Dedoussis, George and Ford, Ian and Frost, Morten and Goltzman, David and Gonz{\'a}lez-Mac{\'\i}as, Jes{\'u}s and K{\"a}h{\"o}nen, Mika and Karlsson, Magnus and Khusnutdinova, Elza and Koh, Jung-Min and Kollia, Panagoula and Langdahl, Bente Lomholt and Leslie, William D and Lips, Paul and Ljunggren, Osten and Lorenc, Roman S and Marc, Janja and Mellstr{\"o}m, Dan and Obermayer-Pietsch, Barbara and Olmos, Jos{\'e} M and Pettersson-Kymmer, Ulrika and Reid, David M and Riancho, Jos{\'e} A and Ridker, Paul M and Rousseau, Fran{\c c}ois and Slagboom, P Eline and Tang, Nelson L S and Urreizti, Roser and Van Hul, Wim and Viikari, Jorma and Zarrabeitia, Mar{\'\i}a T and Aulchenko, Yurii S and Castano-Betancourt, Martha and Grundberg, Elin and Herrera, Lizbeth and Ingvarsson, Thorvaldur and Johannsdottir, Hrefna and Kwan, Tony and Li, Rui and Luben, Robert and Medina-G{\'o}mez, Carolina and Palsson, Stefan Th and Reppe, Sjur and Rotter, Jerome I and Sigurdsson, Gunnar and van Meurs, Joyce B J and Verlaan, Dominique and Williams, Frances M K and Wood, Andrew R and Zhou, Yanhua and Gautvik, Kaare M and Pastinen, Tomi and Raychaudhuri, Soumya and Cauley, Jane A and Chasman, Daniel I and Clark, Graeme R and Cummings, Steven R and Danoy, Patrick and Dennison, Elaine M and Eastell, Richard and Eisman, John A and Gudnason, Vilmundur and Hofman, Albert and Jackson, Rebecca D and Jones, Graeme and Jukema, J Wouter and Khaw, Kay-Tee and Lehtim{\"a}ki, Terho and Liu, Yongmei and Lorentzon, Mattias and McCloskey, Eugene and Mitchell, Braxton D and Nandakumar, Kannabiran and Nicholson, Geoffrey C and Oostra, Ben A and Peacock, Munro and Pols, Huibert A P and Prince, Richard L and Raitakari, Olli and Reid, Ian R and Robbins, John and Sambrook, Philip N and Sham, Pak Chung and Shuldiner, Alan R and Tylavsky, Frances A and van Duijn, Cornelia M and Wareham, Nick J and Cupples, L Adrienne and Econs, Michael J and Evans, David M and Harris, Tamara B and Kung, Annie Wai Chee and Psaty, Bruce M and Reeve, Jonathan and Spector, Timothy D and Streeten, Elizabeth A and Zillikens, M Carola and Thorsteinsdottir, Unnur and Ohlsson, Claes and Karasik, David and Richards, J Brent and Brown, Matthew A and Stefansson, Kari and Uitterlinden, Andr{\'e} G and Ralston, Stuart H and Ioannidis, John P A and Kiel, Douglas P and Rivadeneira, Fernando}
}
