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Grant Details

Grant Number: 5R01CA124558-05 Interpret this number
Primary Investigator: Zheng, Wei
Organization: Vanderbilt University
Project Title: Genetic Factors for Breast Cancer a Genome Wide Study
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): Breast cancer is the most common malignancy among women in many parts of the world. Genetic factors play an important role in the etiology of breast cancer. However, to date, only a few breast cancer susceptibility genes have been identified, and they explain only a very small fraction of breast cancer cases in the general population. A large number of candidate-gene studies have been conducted over the past 10 years. These studies, however, are clearly inadequate to fully uncover the genetic basis of breast cancer. With recent significant advances in high-throughput genotyping technologies, it has become feasible to conduct genome-wide association (GWA) studies to systematically evaluate genetic risk factors for breast cancer. The multi-phase GWA study proposed in this application will be built upon the resources established in two large, on-going studies funded by NCI, the Shanghai Breast Cancer Study (R01 CA64277) a population-based case-control study, and the Shanghai Women's Health Study (RO1 CA70867) a population-based prospective cohort study. Approximately 8,000 breast cancer cases and controls will be included in this proposed study. In the first phase of the study, we will conduct a GWA scan in 1,000 cases and 1,000 controls using the Illumina HumanHap550 BeadChip. We will then select the 10,600 most promising SNPs for a validation study in an independent sample of 1500 cases and 1500 controls. All promising SNPs will be further validated using data from 1000 cases and 2000 controls selected from the prospective Shanghai Women's Health Study. The parent projects of this newly-proposed study have been exceptionally well-conducted with a strong methodology. The feasibility and utility of the proposed study have been clearly demonstrated in our pilot study. The study is unique and has many unique features that facilitate a rigorous evaluation of breast cancer genetic factors. The results from the study will be valuable in identifying high risk women for primary and secondary prevention of breast cancer. PUBLIC HEALTH RELEVANCE: Genetic factors and gene-environment interaction are believed to cause most breast cancers, yet only a small number of cases are explained by genetic factors identified thus far. The large epidemiologic study we propose will comprehensively evaluate genetic markers in relation to breast cancer risk. This study will generate valuable results for the identification of high-risk women for the primary and secondary prevention of breast cancer.

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Publications

Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1.
Authors: Cai Q, Zhang B, Sung H, Low SK, Kweon SS, Lu W, Shi J, Long J, Wen W, Choi JY, Noh DY, Shen CY, Matsuo K, Teo SH, Kim MK, Khoo US, Iwasaki M, Hartman M, Takahashi A, Ashikawa K, Matsuda K, Shin MH, Park MH, Zheng Y, Xiang YB, Ji BT, Park SK, Wu PE, Hsiung CN, Ito H, Kasuga Y, Kang P, Mariapun S, Ahn SH, Kang HS, Chan KY, Man EP, Iwata H, Tsugane S, Miao H, Liao J, Nakamura Y, Kubo M, DRIVE GAME-ON Consortium, Delahanty RJ, Zhang Y, Li B, Li C, Gao YT, Shu XO, Kang D, Zheng W
Source: Nat Genet, 2014 Aug;46(8), p. 886-90.
EPub date: 2014 Jul 20.
PMID: 25038754
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Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.
Authors: Wen W, Zheng W, Okada Y, Takeuchi F, Tabara Y, Hwang JY, Dorajoo R, Li H, Tsai FJ, Yang X, He J, Wu Y, He M, Zhang Y, Liang J, Guo X, Sheu WH, Delahanty R, Guo X, Kubo M, Yamamoto K, Ohkubo T, Go MJ, Liu JJ, Gan W, Chen CC, Gao Y, Li S, Lee NR, Wu C, Zhou X, Song H, Yao J, Lee IT, Long J, Tsunoda T, Akiyama K, Takashima N, Cho YS, Ong RT, Lu L, Chen CH, Tan A, Rice TK, Adair LS, Gui L, Allison M, Lee WJ, Cai Q, Isomura M, Umemura S, Kim YJ, Seielstad M, Hixson J, Xiang YB, Isono M, Kim BJ, Sim X, Lu W, Nabika T, Lee J, Lim WY, Gao YT, Takayanagi R, Kang DH, Wong TY, Hsiung CA, Wu IC, Juang JM, Shi J, Choi BY, Aung T, Hu F, Kim MK, Lim WY, Wang TD, Shin MH, Lee J, Ji BT, Lee YH, Young TL, Shin DH, Chun BY, Cho MC, Han BG, Hwu CM, Assimes TL, Absher D, Yan X, Kim E, Kuo JZ, Kwon S, Taylor KD, Chen YD, Rotter JI, Qi L, Zhu D, Wu T, Mohlke KL, Gu D, Mo Z, Wu JY, Lin X, Miki T, Tai ES, Lee JY, Kato N, Shu XO, Tanaka T
Source: Hum Mol Genet, 2014 Oct 15;23(20), p. 5492-504.
EPub date: 2014 May 26.
PMID: 24861553
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Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
Authors: Zhang B, Jia WH, Matsuda K, Kweon SS, Matsuo K, Xiang YB, Shin A, Jee SH, Kim DH, Cai Q, Long J, Shi J, Wen W, Yang G, Zhang Y, Li C, Li B, Guo Y, Ren Z, Ji BT, Pan ZZ, Takahashi A, Shin MH, Matsuda F, Gao YT, Oh JH, Kim S, Ahn YO, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Chan AT, Chang-Claude J, Slattery ML, Colorectal Transdisciplinary (CORECT) Study, Gruber SB, Schumacher FR, Stenzel SL, Colon Cancer Family Registry (CCFR), Casey G, Kim HR, Jeong JY, Park JW, Li HL, Hosono S, Cho SH, Kubo M, Shu XO, Zeng YX, Zheng W
Source: Nat Genet, 2014 Jun;46(6), p. 533-42.
EPub date: 2014 May 18.
PMID: 24836286
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Rare coding variants and breast cancer risk: evaluation of susceptibility Loci identified in genome-wide association studies.
Authors: Zhang Y, Long J, Lu W, Shu XO, Cai Q, Zheng Y, Li C, Li B, Gao YT, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2014 Apr;23(4), p. 622-8.
EPub date: 2014 Jan 27.
PMID: 24470074
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Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in East Asians.
Authors: Zhang B, Jia WH, Matsuo K, Shin A, Xiang YB, Matsuda K, Jee SH, Kim DH, Cheah PY, Ren Z, Cai Q, Long J, Shi J, Wen W, Yang G, Ji BT, Pan ZZ, Matsuda F, Gao YT, Oh JH, Ahn YO, Kubo M, Thean LF, Park EJ, Li HL, Park JW, Jo J, Jeong JY, Hosono S, Nakamura Y, Shu XO, Zeng YX, Zheng W
Source: Int J Cancer, 2014 Aug 15;135(4), p. 948-55.
EPub date: 2014 Jan 29.
PMID: 24448986
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Genetic variation in the peroxisome proliferator-activated receptor (PPAR) and peroxisome proliferator-activated receptor gamma co-activator 1 (PGC1) gene families and type 2 diabetes.
Authors: Villegas R, Williams SM, Gao YT, Long J, Shi J, Cai H, Li H, Chen CC, Tai ES, AGEN-T2D Consortium, Hu F, Cai Q, Zheng W, Shu XO
Source: Ann Hum Genet, 2014 Jan;78(1), p. 23-32.
PMID: 24359475
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No association between genetic variants in angiogenesis and inflammation pathway genes and breast cancer survival among Chinese women.
Authors: Dorjgochoo T, Zheng Y, Gao YT, Ma X, Long J, Bao P, Zhang B, Wen W, Lu W, Zheng W, Shu XO, Beeghly-Fadiel A
Source: Cancer Epidemiol, 2013 Oct;37(5), p. 619-24.
EPub date: 2013 Jul 11.
PMID: 23850146
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New breast cancer risk variant discovered at 10q25 in East Asian women.
Authors: Shi J, Sung H, Zhang B, Lu W, Choi JY, Xiang YB, Kim MK, Iwasaki M, Long J, Ji BT, Park SK, Zheng Y, Tsugane S, Yoo KY, Wang W, Noh DY, Han W, Kim SW, Lee MH, Lee JW, Lee JY, Shen CY, Matsuo K, Ahn SH, Gao YT, Shu XO, Cai Q, Kang D, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2013 Jul;22(7), p. 1297-303.
EPub date: 2013 May 15.
PMID: 23677579
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Evaluating GWAS-identified SNPs for age at natural menopause among chinese women.
Authors: Shen C, Delahanty RJ, Gao YT, Lu W, Xiang YB, Zheng Y, Cai Q, Zheng W, Shu XO, Long J
Source: PLoS One, 2013;8(3), p. e58766.
EPub date: 2013 Mar 25.
PMID: 23536822
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Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls.
Authors: Zheng W, Zhang B, Cai Q, Sung H, Michailidou K, Shi J, Choi JY, Long J, Dennis J, Humphreys MK, Wang Q, Lu W, Gao YT, Li C, Cai H, Park SK, Yoo KY, Noh DY, Han W, Dunning AM, Benitez J, Vincent D, Bacot F, Tessier D, Kim SW, Lee MH, Lee JW, Lee JY, Xiang YB, Zheng Y, Wang W, Ji BT, Matsuo K, Ito H, Iwata H, Tanaka H, Wu AH, Tseng CC, Van Den Berg D, Stram DO, Teo SH, Yip CH, Kang IN, Wong TY, Shen CY, Yu JC, Huang CS, Hou MF, Hartman M, Miao H, Lee SC, Putti TC, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Sangrajrang S, Shen H, Chen K, Wu PE, Ren Z, Haiman CA, Sueta A, Kim MK, Khoo US, Iwasaki M, Pharoah PD, Wen W, Hall P, Shu XO, Easton DF, Kang D
Source: Hum Mol Genet, 2013 Jun 15;22(12), p. 2539-50.
EPub date: 2013 Mar 27.
PMID: 23535825
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Breast cancer susceptibility associated with rs1219648 (fibroblast growth factor receptor 2) and postmenopausal hormone therapy use in a population-based United States study.
Authors: Andersen SW, Trentham-Dietz A, Figueroa JD, Titus LJ, Cai Q, Long J, Hampton JM, Egan KM, Newcomb PA
Source: Menopause, 2013 Mar;20(3), p. 354-8.
PMID: 23435034
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A common deletion in the APOBEC3 genes and breast cancer risk.
Authors: Long J, Delahanty RJ, Li G, Gao YT, Lu W, Cai Q, Xiang YB, Li C, Ji BT, Zheng Y, Ali S, Shu XO, Zheng W
Source: J Natl Cancer Inst, 2013 Apr 17;105(8), p. 573-9.
EPub date: 2013 Feb 14.
PMID: 23411593
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Evaluation of GWAS-identified genetic variants for age at menarche among Chinese women.
Authors: Delahanty RJ, Beeghly-Fadiel A, Long JR, Gao YT, Lu W, Xiang YB, Zheng Y, Ji BT, Wen WQ, Cai QY, Zheng W, Shu XO
Source: Hum Reprod, 2013 Apr;28(4), p. 1135-43.
EPub date: 2013 Feb 12.
PMID: 23406970
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Steps to ensure accuracy in genotype and SNP calling from Illumina sequencing data.
Authors: Liu Q, Guo Y, Li J, Long J, Zhang B, Shyr Y
Source: BMC Genomics, 2012;13 Suppl 8, p. S8.
EPub date: 2012 Dec 17.
PMID: 23281772
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No association between ovarian cancer susceptibility variants and breast cancer risk among Chinese women.
Authors: Ma X, Cai Q, Delahanty RJ, Shu XO, Zhang B, Lu W, Gao YT, Zheng W, Long J, Beeghly-Fadiel A
Source: Cancer Epidemiol Biomarkers Prev, 2013 Mar;22(3), p. 467-9.
EPub date: 2013 Jan 4.
PMID: 23292081
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Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis.
Authors: Peters U, Jiao S, Schumacher FR, Hutter CM, Aragaki AK, Baron JA, Berndt SI, Bézieau S, Brenner H, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Casey G, Chan AT, Chang-Claude J, Chanock SJ, Chen LS, Coetzee GA, Coetzee SG, Conti DV, Curtis KR, Duggan D, Edwards T, Fuchs CS, Gallinger S, Giovannucci EL, Gogarten SM, Gruber SB, Haile RW, Harrison TA, Hayes RB, Henderson BE, Hoffmeister M, Hopper JL, Hudson TJ, Hunter DJ, Jackson RD, Jee SH, Jenkins MA, Jia WH, Kolonel LN, Kooperberg C, Küry S, Lacroix AZ, Laurie CC, Laurie CA, Le Marchand L, Lemire M, Levine D, Lindor NM, Liu Y, Ma J, Makar KW, Matsuo K, Newcomb PA, Potter JD, Prentice RL, Qu C, Rohan T, Rosse SA, Schoen RE, Seminara D, Shrubsole M, Shu XO, Slattery ML, Taverna D, Thibodeau SN, Ulrich CM, White E, Xiang Y, Zanke BW, Zeng YX, Zhang B, Zheng W, Hsu L, Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium
Source: Gastroenterology, 2013 Apr;144(4), p. 799-807.e24.
EPub date: 2012 Dec 22.
PMID: 23266556
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Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer.
Authors: Jia WH, Zhang B, Matsuo K, Shin A, Xiang YB, Jee SH, Kim DH, Ren Z, Cai Q, Long J, Shi J, Wen W, Yang G, Delahanty RJ, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Colon Cancer Family Registry (CCFR), Ji BT, Pan ZZ, Matsuda F, Gao YT, Oh JH, Ahn YO, Park EJ, Li HL, Park JW, Jo J, Jeong JY, Hosono S, Casey G, Peters U, Shu XO, Zeng YX, Zheng W
Source: Nat Genet, 2013 Feb;45(2), p. 191-6.
EPub date: 2012 Dec 23.
PMID: 23263487
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Gene-environment interactions for breast cancer risk among Chinese women: a report from the Shanghai Breast Cancer Genetics Study.
Authors: Li H, Beeghly-Fadiel A, Wen W, Lu W, Gao YT, Xiang YB, Cai Q, Long J, Shi J, Chen K, Zheng Y, Shu XO, Zheng W
Source: Am J Epidemiol, 2013 Jan 15;177(2), p. 161-70.
EPub date: 2012 Dec 6.
PMID: 23221726
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Joint effect of genetic and lifestyle risk factors on type 2 diabetes risk among Chinese men and women.
Authors: Villegas R, Delahanty R, Gao YT, Long J, Williams SM, Xiang YB, Cai H, Li HL, Hu F, Cai Q, Zheng W, Shu XO
Source: PLoS One, 2012;7(11), p. e49464.
EPub date: 2012 Nov 21.
PMID: 23185337
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The effect of strand bias in Illumina short-read sequencing data.
Authors: Guo Y, Li J, Li CI, Long J, Samuels DC, Shyr Y
Source: BMC Genomics, 2012 Nov 24;13, p. 666.
EPub date: 2012 Nov 24.
PMID: 23176052
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Exome sequencing generates high quality data in non-target regions.
Authors: Guo Y, Long J, He J, Li CI, Cai Q, Shu XO, Zheng W, Li C
Source: BMC Genomics, 2012 May 20;13, p. 194.
EPub date: 2012 May 20.
PMID: 22607156
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Pathway analyses identify TGFBR2 as potential breast cancer susceptibility gene: results from a consortium study among Asians.
Authors: Ma X, Beeghly-Fadiel A, Lu W, Shi J, Xiang YB, Cai Q, Shen H, Shen CY, Ren Z, Matsuo K, Khoo US, Iwasaki M, Long J, Zhang B, Ji BT, Zheng Y, Wang W, Hu Z, Liu Y, Wu PE, Shieh YL, Wang S, Xie X, Ito H, Kasuga Y, Chan KY, Iwata H, Tsugane S, Gao YT, Shu XO, Moses HL, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2012 Jul;21(7), p. 1176-84.
EPub date: 2012 Apr 26.
PMID: 22539603
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Genome-wide association study identifies a possible susceptibility locus for endometrial cancer.
Authors: Long J, Zheng W, Xiang YB, Lose F, Thompson D, Tomlinson I, Yu H, Wentzensen N, Lambrechts D, Dörk T, Dubrowinskaja N, Goodman MT, Salvesen HB, Fasching PA, Scott RJ, Delahanty R, Zheng Y, O'Mara T, Healey CS, Hodgson S, Risch H, Yang HP, Amant F, Turmanov N, Schwake A, Lurie G, Trovik J, Beckmann MW, Ashton K, Ji BT, Bao PP, Howarth K, Lu L, Lissowska J, Coenegrachts L, Kaidarova D, Dürst M, Thompson PJ, Krakstad C, Ekici AB, Otton G, Shi J, Zhang B, Gorman M, Brinton L, Coosemans A, Matsuno RK, Halle MK, Hein A, Proietto A, Cai H, Lu W, Dunning A, Easton D, Gao YT, Cai Q, Spurdle AB, Shu XO
Source: Cancer Epidemiol Biomarkers Prev, 2012 Jun;21(6), p. 980-7.
EPub date: 2012 Mar 16.
PMID: 22426144
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Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.
Authors: Long J, Cai Q, Sung H, Shi J, Zhang B, Choi JY, Wen W, Delahanty RJ, Lu W, Gao YT, Shen H, Park SK, Chen K, Shen CY, Ren Z, Haiman CA, Matsuo K, Kim MK, Khoo US, Iwasaki M, Zheng Y, Xiang YB, Gu K, Rothman N, Wang W, Hu Z, Liu Y, Yoo KY, Noh DY, Han BG, Lee MH, Zheng H, Zhang L, Wu PE, Shieh YL, Chan SY, Wang S, Xie X, Kim SW, Henderson BE, Le Marchand L, Ito H, Kasuga Y, Ahn SH, Kang HS, Chan KY, Iwata H, Tsugane S, Li C, Shu XO, Kang DH, Zheng W
Source: PLoS Genet, 2012;8(2), p. e1002532.
EPub date: 2012 Feb 23.
PMID: 22383897
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Replication study for reported SNP associations with breast cancer survival.
Authors: Beeghly-Fadiel A, Zheng W, Lu W, Long J, Zheng Y, Cai H, Gu K, Chen Z, Cai Q, Gao YT, Shu XO
Source: J Cancer Res Clin Oncol, 2012 Jun;138(6), p. 1019-26.
EPub date: 2012 Feb 25.
PMID: 22367361
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Meta-analysis identifies common variants associated with body mass index in east Asians.
Authors: Wen W, Cho YS, Zheng W, Dorajoo R, Kato N, Qi L, Chen CH, Delahanty RJ, Okada Y, Tabara Y, Gu D, Zhu D, Haiman CA, Mo Z, Gao YT, Saw SM, Go MJ, Takeuchi F, Chang LC, Kokubo Y, Liang J, Hao M, Le Marchand L, Zhang Y, Hu Y, Wong TY, Long J, Han BG, Kubo M, Yamamoto K, Su MH, Miki T, Henderson BE, Song H, Tan A, He J, Ng DP, Cai Q, Tsunoda T, Tsai FJ, Iwai N, Chen GK, Shi J, Xu J, Sim X, Xiang YB, Maeda S, Ong RT, Li C, Nakamura Y, Aung T, Kamatani N, Liu JJ, Lu W, Yokota M, Seielstad M, Fann CS, Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Wu JY, Lee JY, Hu FB, Tanaka T, Tai ES, Shu XO
Source: Nat Genet, 2012 Feb 19;44(3), p. 307-11.
EPub date: 2012 Feb 19.
PMID: 22344219
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Novel genetic markers of breast cancer survival identified by a genome-wide association study.
Authors: Shu XO, Long J, Lu W, Li C, Chen WY, Delahanty R, Cheng J, Cai H, Zheng Y, Shi J, Gu K, Wang WJ, Kraft P, Gao YT, Cai Q, Zheng W
Source: Cancer Res, 2012 Mar 1;72(5), p. 1182-9.
EPub date: 2012 Jan 9.
PMID: 22232737
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Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
Authors: Cho YS, Chen CH, Hu C, Long J, Ong RT, Sim X, Takeuchi F, Wu Y, Go MJ, Yamauchi T, Chang YC, Kwak SH, Ma RC, Yamamoto K, Adair LS, Aung T, Cai Q, Chang LC, Chen YT, Gao Y, Hu FB, Kim HL, Kim S, Kim YJ, Lee JJ, Lee NR, Li Y, Liu JJ, Lu W, Nakamura J, Nakashima E, Ng DP, Tay WT, Tsai FJ, Wong TY, Yokota M, Zheng W, Zhang R, Wang C, So WY, Ohnaka K, Ikegami H, Hara K, Cho YM, Cho NH, Chang TJ, Bao Y, Hedman ĊK, Morris AP, McCarthy MI, DIAGRAM Consortium, MuTHER Consortium, Takayanagi R, Park KS, Jia W, Chuang LM, Chan JC, Maeda S, Kadowaki T, Lee JY, Wu JY, Teo YY, Tai ES, Shu XO, Mohlke KL, Kato N, Han BG, Seielstad M
Source: Nat Genet, 2011 Dec 11;44(1), p. 67-72.
EPub date: 2011 Dec 11.
PMID: 22158537
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Genetic variants in vitamin D metabolism-related genes and body mass index: analysis of genome-wide scan data of approximately 7000 Chinese women.
Authors: Dorjgochoo T, Shi J, Gao YT, Long J, Delahanty R, Xiang YB, Cai Q, Shu XO
Source: Int J Obes (Lond), 2012 Sep;36(9), p. 1252-5.
EPub date: 2011 Dec 13.
PMID: 22158264
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