BACKGROUND: Osteoporosis is a common condition among elderly. Genetic mapping studies repeatedly located the distal short arms of X-chromosome as the quantitative trait loci (QTL) for BMD in mice. Fine mapping of a syntenic segment on Xp22 in a Caucasian female population suggested a moderate association between lumbar spine (LS) BMD and 2 intronic SNPs in the Pirin (PIR) gene, which encodes an iron-binding nuclear protein. This study aimed to examine genetic variations in the PIR gene by a comprehensive tagging method and its sex-specific effects on BMD and osteoporotic risk. METHODS: Two thousand men and 2000 women aged 65 or above were recruited from the community. BMDs at the LS, femoral neck, total hip and whole body were measured and followed up at 4-year. Genotyping was performed for tagSNPs of PIR gene including adjacent regions, and the PIR haplotypes were inferred using PHASE program. RESULTS: Analysis by linear regression showed a significant association between SNP rs5935970 and LS-BMD, while haplotype T-T-A was significantly associated with BMD of all measured sites. However, none of such associations were found in men. Linear Mixed Model also confirmed the same sex-specific and site-specific effect for longitudinal BMD changes. CONCLUSION: In addition to confirming the association between BMDs and the PIR gene, we also revealed that this finding is sex-specific, possibly due to an X-linked effect. This study demonstrated the importance of considering sex and genetic interactions in studies of disease predisposition and complex traits. (c) 2009 Elsevier Inc. All rights reserved.
BACKGROUND:Osteoporosis is a common condition among elderly. Genetic mapping studies repeatedly located the distal short arms of X-chromosome as the quantitative trait loci (QTL) for BMD in mice. Fine mapping of a syntenic segment on Xp22 in a Caucasian female population suggested a moderate association between lumbar spine (LS) BMD and 2 intronic SNPs in the Pirin (PIR) gene, which encodes an iron-binding nuclear protein. This study aimed to examine genetic variations in the PIR gene by a comprehensive tagging method and its sex-specific effects on BMD and osteoporotic risk. METHODS: Two thousand men and 2000 women aged 65 or above were recruited from the community. BMDs at the LS, femoral neck, total hip and whole body were measured and followed up at 4-year. Genotyping was performed for tagSNPs of PIR gene including adjacent regions, and the PIR haplotypes were inferred using PHASE program. RESULTS: Analysis by linear regression showed a significant association between SNP rs5935970 and LS-BMD, while haplotype T-T-A was significantly associated with BMD of all measured sites. However, none of such associations were found in men. Linear Mixed Model also confirmed the same sex-specific and site-specific effect for longitudinal BMD changes. CONCLUSION: In addition to confirming the association between BMDs and the PIR gene, we also revealed that this finding is sex-specific, possibly due to an X-linked effect. This study demonstrated the importance of considering sex and genetic interactions in studies of disease predisposition and complex traits. (c) 2009 Elsevier Inc. All rights reserved.
Authors: Unnur Styrkarsdottir; Hannes Helgason; Asgeir Sigurdsson; Gudmundur L Norddahl; Arna B Agustsdottir; Louise N Reynard; Amanda Villalvilla; Gisli H Halldorsson; Aslaug Jonasdottir; Audur Magnusdottir; Asmundur Oddson; Gerald Sulem; Florian Zink; Gardar Sveinbjornsson; Agnar Helgason; Hrefna S Johannsdottir; Anna Helgadottir; Hreinn Stefansson; Solveig Gretarsdottir; Thorunn Rafnar; Ina S Almdahl; Anne Brækhus; Tormod Fladby; Geir Selbæk; Farhad Hosseinpanah; Fereidoun Azizi; Jung Min Koh; Nelson L S Tang; Maryam S Daneshpour; Jose I Mayordomo; Corrine Welt; Peter S Braund; Nilesh J Samani; Lambertus A Kiemeney; L Stefan Lohmander; Claus Christiansen; Ole A Andreassen; Olafur Magnusson; Gisli Masson; Augustine Kong; Ingileif Jonsdottir; Daniel Gudbjartsson; Patrick Sulem; Helgi Jonsson; John Loughlin; Thorvaldur Ingvarsson; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2017-03-20 Impact factor: 38.330
Authors: Ching-Ti Liu; Karol Estrada; Laura M Yerges-Armstrong; Najaf Amin; Evangelos Evangelou; Guo Li; Ryan L Minster; Melanie A Carless; Candace M Kammerer; Ling Oei; Yanhua Zhou; Nerea Alonso; Zoe Dailiana; Joel Eriksson; Natalia García-Giralt; Sylvie Giroux; Lise Bjerre Husted; Rita I Khusainova; Theodora Koromila; Annie Waichee Kung; Joshua R Lewis; Laura Masi; Simona Mencej-Bedrac; Xavier Nogues; Millan S Patel; Janez Prezelj; J Brent Richards; Pak Chung Sham; Timothy Spector; Liesbeth Vandenput; Su-Mei Xiao; Hou-Feng Zheng; Kun Zhu; Susana Balcells; Maria Luisa Brandi; Morten Frost; David Goltzman; Jesús González-Macías; Magnus Karlsson; Elza K Khusnutdinova; Panagoula Kollia; Bente Lomholt Langdahl; Osten Ljunggren; Mattias Lorentzon; Janja Marc; Dan Mellström; Claes Ohlsson; José M Olmos; Stuart H Ralston; José A Riancho; François Rousseau; Roser Urreizti; Wim Van Hul; María T Zarrabeitia; Martha Castano-Betancourt; Serkalem Demissie; Elin Grundberg; Lizbeth Herrera; Tony Kwan; Carolina Medina-Gómez; Tomi Pastinen; Gunnar Sigurdsson; Gudmar Thorleifsson; Joyce Bj Vanmeurs; John Blangero; Albert Hofman; Yongmei Liu; Braxton D Mitchell; Jeffrey R O'Connell; Ben A Oostra; Jerome I Rotter; Kari Stefansson; Elizabeth A Streeten; Unnur Styrkarsdottir; Unnur Thorsteinsdottir; Frances A Tylavsky; Andre Uitterlinden; Jane A Cauley; Tamara B Harris; John Pa Ioannidis; Bruce M Psaty; John A Robbins; M Carola Zillikens; Cornelia M Vanduijn; Richard L Prince; David Karasik; Fernando Rivadeneira; Douglas P Kiel; L Adrienne Cupples; Yi-Hsiang Hsu Journal: J Bone Miner Res Date: 2012-10 Impact factor: 6.741
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Authors: Unnur Styrkarsdottir; Gudmar Thorleifsson; Sigurjon A Gudjonsson; Asgeir Sigurdsson; Jacqueline R Center; Seung Hun Lee; Tuan V Nguyen; Timothy C Y Kwok; Jenny S W Lee; Suzanne C Ho; Jean Woo; Ping-C Leung; Beom-Jun Kim; Thorunn Rafnar; Lambertus A Kiemeney; Thorvaldur Ingvarsson; Jung-Min Koh; Nelson L S Tang; John A Eisman; Claus Christiansen; Gunnar Sigurdsson; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Commun Date: 2016-01-06 Impact factor: 14.919