Replication study of candidate genes/loci associated with osteoporosis based on genome-wide screening

go back to reference [No authors listed] (1993) Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 94:646–650 [No authors listed] (1993) Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 94:646–650

go back to reference Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767CrossRefPubMed Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767CrossRefPubMed

go back to reference Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B, Oden A, Zethraeus N, Pfleger B, Khaltaev N (2005) Assessment of fracture risk. Osteoporos Int 16:581–589CrossRefPubMed Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B, Oden A, Zethraeus N, Pfleger B, Khaltaev N (2005) Assessment of fracture risk. Osteoporos Int 16:581–589CrossRefPubMed

go back to reference Deng HW, Chen WM, Conway T, Zhou Y, Davies KM, Stegman MR, Deng H, Recker RR (2000) Determination of bone mineral density of the hip and spine in human pedigrees by genetic and lifestyle factors. Genet Epidemiol 19:160–177CrossRefPubMed Deng HW, Chen WM, Conway T, Zhou Y, Davies KM, Stegman MR, Deng H, Recker RR (2000) Determination of bone mineral density of the hip and spine in human pedigrees by genetic and lifestyle factors. Genet Epidemiol 19:160–177CrossRefPubMed

go back to reference Liu YJ, Shen H, Xiao P, Xiong DH, Li LH, Recker RR, Deng HW (2006) Molecular genetic studies of gene identification for osteoporosis: a 2004 update. J Bone Miner Res 21:1511–1535CrossRefPubMed Liu YJ, Shen H, Xiao P, Xiong DH, Li LH, Recker RR, Deng HW (2006) Molecular genetic studies of gene identification for osteoporosis: a 2004 update. J Bone Miner Res 21:1511–1535CrossRefPubMed

go back to reference Kiel DP, Demissie S, Dupuis J, Lunetta KL, Murabito JM, Karasik D (2007) Genome-wide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet 8:S14CrossRefPubMed Kiel DP, Demissie S, Dupuis J, Lunetta KL, Murabito JM, Karasik D (2007) Genome-wide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet 8:S14CrossRefPubMed

go back to reference Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, Jonsdottir T, Saemundsdottir J, Center JR, Nguyen TV, Bagger Y, Gulcher JR, Eisman JA, Christiansen C, Sigurdsson G, Kong A, Thorsteinsdottir U, Stefansson K (2008) Multiple genetic loci for bone mineral density and fractures. N Engl J Med 358:2355–2365CrossRefPubMed Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, Jonsdottir T, Saemundsdottir J, Center JR, Nguyen TV, Bagger Y, Gulcher JR, Eisman JA, Christiansen C, Sigurdsson G, Kong A, Thorsteinsdottir U, Stefansson K (2008) Multiple genetic loci for bone mineral density and fractures. N Engl J Med 358:2355–2365CrossRefPubMed

go back to reference Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, Valdes AM, Arp P, Whittaker P, Verlaan DJ, Jhamai M, Kumanduri V, Moorhouse M, van Meurs JB, Hofman A, Pols HA, Hart D, Zhai G, Kato BS, Mullin BH, Zhang F, Deloukas P, Uitterlinden AG, Spector TD (2008) Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 371:1505–1512CrossRefPubMed Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, Valdes AM, Arp P, Whittaker P, Verlaan DJ, Jhamai M, Kumanduri V, Moorhouse M, van Meurs JB, Hofman A, Pols HA, Hart D, Zhai G, Kato BS, Mullin BH, Zhang F, Deloukas P, Uitterlinden AG, Spector TD (2008) Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 371:1505–1512CrossRefPubMed

go back to reference Arden NK, Baker J, Hogg C, Baan K, Spector TD (1996) The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 11:530–534 Arden NK, Baker J, Hogg C, Baan K, Spector TD (1996) The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 11:530–534

go back to reference Hannan MT, Felson DT, Dawson-Hughes B, Tucker KL, Cupples LA, Wilson PW, Kiel DP (2000) Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 15:710–720 Hannan MT, Felson DT, Dawson-Hughes B, Tucker KL, Cupples LA, Wilson PW, Kiel DP (2000) Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 15:710–720

go back to reference Di X, Matsuzaki H, Webster TA, Hubbell E, Liu G, Dong S, Bartell D, Huang J, Chiles R, Yang G, Shen MM, Kulp D, Kennedy GC, Mei R, Jones KW, Cawley S (2005) Dynamic model based algorithms for screening and genotyping over 100 K SNPs on oligonucleotide microarrays. Bioinformatics (Oxford, England) 21:1958–1963CrossRef Di X, Matsuzaki H, Webster TA, Hubbell E, Liu G, Dong S, Bartell D, Huang J, Chiles R, Yang G, Shen MM, Kulp D, Kennedy GC, Mei R, Jones KW, Cawley S (2005) Dynamic model based algorithms for screening and genotyping over 100 K SNPs on oligonucleotide microarrays. Bioinformatics (Oxford, England) 21:1958–1963CrossRef

go back to reference Rabbee N, Speed TP (2006) A genotype calling algorithm for affymetrix SNP arrays. Bioinformatics (Oxford, England) 22:7–12CrossRef Rabbee N, Speed TP (2006) A genotype calling algorithm for affymetrix SNP arrays. Bioinformatics (Oxford, England) 22:7–12CrossRef

go back to reference Fisher RA (1925) The resemblance between twins, a statistical examination of Lauterbach's Measurements. Genetics 10:569–579PubMed Fisher RA (1925) The resemblance between twins, a statistical examination of Lauterbach's Measurements. Genetics 10:569–579PubMed

go back to reference Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575CrossRefPubMed Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575CrossRefPubMed

go back to reference Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959PubMed Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959PubMed

go back to reference Devlin B, Roeder K (1999) Genomic control for association studies. Biometrics 55:997–1004CrossRefPubMed Devlin B, Roeder K (1999) Genomic control for association studies. Biometrics 55:997–1004CrossRefPubMed

go back to reference Boerboom D, Pilon N, Behdjani R, Silversides DW, Sirois J (2000) Expression and regulation of transcripts encoding two members of the NR5A nuclear receptor subfamily of orphan nuclear receptors, steroidogenic factor-1 and NR5A2, in equine ovarian cells during the ovulatory process. Endocrinology 141:4647–4656CrossRefPubMed Boerboom D, Pilon N, Behdjani R, Silversides DW, Sirois J (2000) Expression and regulation of transcripts encoding two members of the NR5A nuclear receptor subfamily of orphan nuclear receptors, steroidogenic factor-1 and NR5A2, in equine ovarian cells during the ovulatory process. Endocrinology 141:4647–4656CrossRefPubMed

go back to reference Nishimura M, Naito S, Yokoi T (2004) Tissue-specific mRNA expression profiles of human nuclear receptor subfamilies. Drug Metab Pharmacokinet 19:135–149CrossRefPubMed Nishimura M, Naito S, Yokoi T (2004) Tissue-specific mRNA expression profiles of human nuclear receptor subfamilies. Drug Metab Pharmacokinet 19:135–149CrossRefPubMed

go back to reference Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA 2nd, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L (2002) Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 157:303–314CrossRefPubMed Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA 2nd, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L (2002) Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 157:303–314CrossRefPubMed

go back to reference Krishnan V, Bryant HU, Macdougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202–1209CrossRefPubMed Krishnan V, Bryant HU, Macdougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202–1209CrossRefPubMed

go back to reference Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Jèuppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513–523CrossRefPubMed Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Jèuppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513–523CrossRefPubMed

go back to reference Xiong DH, Lei SF, Yang F, Wang L, Peng YM, Wang W, Recker RR, Deng HW (2007) Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 22:385–393 Xiong DH, Lei SF, Yang F, Wang L, Peng YM, Wang W, Recker RR, Deng HW (2007) Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 22:385–393

go back to reference Koay MA, Woon PY, Zhang Y, Miles LJ, Duncan EL, Ralston SH, Compston JE, Cooper C, Keen R, Langdahl BL, MacLelland A, O'Riordan J, Pols HA, Reid DM, Uitterlinden AG, Wass JA, Brown MA (2004) Influence of LRP5 polymorphisms on normal variation in BMD. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 19:1619–1627 Koay MA, Woon PY, Zhang Y, Miles LJ, Duncan EL, Ralston SH, Compston JE, Cooper C, Keen R, Langdahl BL, MacLelland A, O'Riordan J, Pols HA, Reid DM, Uitterlinden AG, Wass JA, Brown MA (2004) Influence of LRP5 polymorphisms on normal variation in BMD. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 19:1619–1627

go back to reference Grundberg E, Lau EM, Lorentzson M, Karlsson M, Holmberg A, Groop L, Mellstrèom D, Orwoll E, Mallmin H, Ohlsson C, Ljunggren O, Akesson K (2008) Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men. Osteoporos Int 19:829–837CrossRefPubMed Grundberg E, Lau EM, Lorentzson M, Karlsson M, Holmberg A, Groop L, Mellstrèom D, Orwoll E, Mallmin H, Ohlsson C, Ljunggren O, Akesson K (2008) Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men. Osteoporos Int 19:829–837CrossRefPubMed

go back to reference Agueda L, Bustamante M, Jurado S, Garcia-Giralt N, Ciria M, Salâo G, Carreras R, Noguâes X, Mellibovsky L, Dâiez-Pâerez A, Grinberg D, Balcells S (2008) A haplotype-based analysis of the LRP5 gene in relation to osteoporosis phenotypes in Spanish postmenopausal women. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 23:1954–1963 Agueda L, Bustamante M, Jurado S, Garcia-Giralt N, Ciria M, Salâo G, Carreras R, Noguâes X, Mellibovsky L, Dâiez-Pâerez A, Grinberg D, Balcells S (2008) A haplotype-based analysis of the LRP5 gene in relation to osteoporosis phenotypes in Spanish postmenopausal women. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 23:1954–1963

go back to reference Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346:1513–1521CrossRefPubMed Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346:1513–1521CrossRefPubMed

go back to reference Johnson ML (2004) The high bone mass family—the role of Wnt/Lrp5 signaling in the regulation of bone mass. J Musculoskelet Neuronal Interact 4:135–138PubMed Johnson ML (2004) The high bone mass family—the role of Wnt/Lrp5 signaling in the regulation of bone mass. J Musculoskelet Neuronal Interact 4:135–138PubMed

go back to reference Tran BN, Nguyen ND, Eisman JA, Nguyen TV (2008) Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis. BMC medical genetics 9:55CrossRefPubMed Tran BN, Nguyen ND, Eisman JA, Nguyen TV (2008) Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis. BMC medical genetics 9:55CrossRefPubMed

go back to reference Kiel DP, Ferrari SL, Cupples LA, Karasik D, Manen D, Imamovic A, Herbert AG, Dupuis J (2007) Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men. Bone 40:587–596CrossRefPubMed Kiel DP, Ferrari SL, Cupples LA, Karasik D, Manen D, Imamovic A, Herbert AG, Dupuis J (2007) Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men. Bone 40:587–596CrossRefPubMed

go back to reference Guo YF, Xiong DH, Shen H, Zhao LJ, Xiao P, Guo Y, Wang W, Yang TL, Recker RR, Deng HW (2006) Polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study. J Med Genet 43:798–803CrossRefPubMed Guo YF, Xiong DH, Shen H, Zhao LJ, Xiao P, Guo Y, Wang W, Yang TL, Recker RR, Deng HW (2006) Polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study. J Med Genet 43:798–803CrossRefPubMed

go back to reference Fujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, Takada S, Kim DH, Ioka RX, Ono M, Tomoyori H, Okubo M, Murase T, Kamataki A, Yamamoto J, Magoori K, Takahashi S, Miyamoto Y, Oishi H, Nose M, Okazaki M, Usui S, Imaizumi K, Yanagisawa M, Sakai J, Yamamoto TT (2003) Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proc Natl Acad Sci U S A 100:229–234CrossRefPubMed Fujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, Takada S, Kim DH, Ioka RX, Ono M, Tomoyori H, Okubo M, Murase T, Kamataki A, Yamamoto J, Magoori K, Takahashi S, Miyamoto Y, Oishi H, Nose M, Okazaki M, Usui S, Imaizumi K, Yanagisawa M, Sakai J, Yamamoto TT (2003) Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proc Natl Acad Sci U S A 100:229–234CrossRefPubMed

go back to reference Venteclef N, Haroniti A, Tousaint JJ, Talianidis I, Delerive P (2008) Regulation of anti-atherogenic apolipoprotein M gene expression by the orphan nuclear receptor LRH-1. J Biol Chem 283:3694–3701CrossRefPubMed Venteclef N, Haroniti A, Tousaint JJ, Talianidis I, Delerive P (2008) Regulation of anti-atherogenic apolipoprotein M gene expression by the orphan nuclear receptor LRH-1. J Biol Chem 283:3694–3701CrossRefPubMed

go back to reference Francis GA, Fayard E, Picard F, Auwerx J (2003) Nuclear receptors and the control of metabolism. Annu Rev Physiol 65:261–311CrossRefPubMed Francis GA, Fayard E, Picard F, Auwerx J (2003) Nuclear receptors and the control of metabolism. Annu Rev Physiol 65:261–311CrossRefPubMed

go back to reference Ory DS (2004) Nuclear receptor signaling in the control of cholesterol homeostasis: have the orphans found a home? Circ Res 95:660–670CrossRefPubMed Ory DS (2004) Nuclear receptor signaling in the control of cholesterol homeostasis: have the orphans found a home? Circ Res 95:660–670CrossRefPubMed

go back to reference Adami S, Braga V, Zamboni M, Gatti D, Rossini M, Bakri J, Battaglia E (2004) Relationship between lipids and bone mass in 2 cohorts of healthy women and men. Calcif Tissue Int 74:136–142CrossRefPubMed Adami S, Braga V, Zamboni M, Gatti D, Rossini M, Bakri J, Battaglia E (2004) Relationship between lipids and bone mass in 2 cohorts of healthy women and men. Calcif Tissue Int 74:136–142CrossRefPubMed

go back to reference Dennison EM, Syddall HE, Aihie Sayer A, Martin HJ, Cooper C (2007) Lipid profile, obesity and bone mineral density: the Hertfordshire Cohort Study. QJM 100:297–303CrossRefPubMed Dennison EM, Syddall HE, Aihie Sayer A, Martin HJ, Cooper C (2007) Lipid profile, obesity and bone mineral density: the Hertfordshire Cohort Study. QJM 100:297–303CrossRefPubMed

go back to reference Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science (New York, NY) 273:1516–1517 Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science (New York, NY) 273:1516–1517

go back to reference Freimer NB, Sabatti C (2007) Human genetics: variants in common diseases. Nature 445:828–830CrossRefPubMed Freimer NB, Sabatti C (2007) Human genetics: variants in common diseases. Nature 445:828–830CrossRefPubMed

go back to reference Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G, Hirschhorn JN, Abecasis G, Altshuler D, Bailey-Wilson JE, Brooks LD, Cardon LR, Daly M, Donnelly P, Fraumeni JF Jr, Freimer NB, Gerhard DS, Gunter C, Guttmacher AE, Guyer MS, Harris EL, Hoh J, Hoover R, Kong CA, Merikangas KR, Morton CC, Palmer LJ, Phimister EG, Rice JP, Roberts J, Rotimi C, Tucker MA, Vogan KJ, Wacholder S, Wijsman EM, Winn DM, Collins FS (2007) Replicating genotype–phenotype associations. Nature 447:655–660CrossRefPubMed Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G, Hirschhorn JN, Abecasis G, Altshuler D, Bailey-Wilson JE, Brooks LD, Cardon LR, Daly M, Donnelly P, Fraumeni JF Jr, Freimer NB, Gerhard DS, Gunter C, Guttmacher AE, Guyer MS, Harris EL, Hoh J, Hoover R, Kong CA, Merikangas KR, Morton CC, Palmer LJ, Phimister EG, Rice JP, Roberts J, Rotimi C, Tucker MA, Vogan KJ, Wacholder S, Wijsman EM, Winn DM, Collins FS (2007) Replicating genotype–phenotype associations. Nature 447:655–660CrossRefPubMed

go back to reference Ioannidis JP (2007) Non-replication and inconsistency in the genome-wide association setting. Hum Hered 64:203–213CrossRefPubMed Ioannidis JP (2007) Non-replication and inconsistency in the genome-wide association setting. Hum Hered 64:203–213CrossRefPubMed