title: Bivariate genome-wide association study suggests fatty acid desaturase genes and cadherin DCHS2 for variation of both compressive strength index and appendicular lean mass in males.
abstract: Compressive strength index (CSI) is a newly established index for predicting hip fracture, the most serious consequence of osteoporosis. Appendicular lean mass (ALM), which influences skeletal strength of the lower limbs, is another trait associated with the risk of hip fracture. In this study, we performed a bivariate genome-wide association study (GWAS) to identify new candidate genes responsible for both CSI and ALM. In our discovery sample of 1627 unrelated Chinese subjects (802 males and 825 females), we scanned 909,509 SNPs using the Affymetrix Human Genome SNP 6.0 genotyping array. We successfully replicated our results in a sample of 2286 Caucasian subjects (558 males and 1728 females). The results indicated that five SNPs (rs174583, rs174577, rs174549, rs174548, rs7672337) in the FADS1, FADS2, and DCHS2 genes had significant bivariate associations with CSI and ALM in male subjects for both the GWAS discovery (with P<8.42×10(-6)) and the Caucasian sample (with P<0.07). We performed further replication analysis in a 2nd Caucasian sample with 501 Caucasian male subjects, using Affymetrix 500k arrays, and found that two of the above SNPs (rs174548 and rs174549, P=0.07) had bivariate associations with both CSI and ALM in males; the other 3 SNPs were not typed with the 500k array. The above findings suggest that the 3 genes, FADS1, FADS2, and DCHS2, containing these SNPs might play dual roles influencing both CSI and ALM in males. Our findings provide new insights into our understanding of the genetic basis of bone metabolism and the pathogenesis of osteoporosis.
authors.affiliation: Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Yangpu District, Shanghai, PR China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Han
authors.forename: Yufang
authors.initials: Y
authors.lastname: Pei
authors.forename: Yaozhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Shuyan
authors.initials: S
authors.lastname: Wu
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Xiangding
authors.initials: X
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Xuezhen
authors.initials: X
authors.lastname: Zhu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.forename: Hongwen
authors.initials: H
authors.lastname: Deng
mesh_terms: D000328:Adult; D044466:Asian People; D015820:Cadherins / Q000235:genetics*; D019245:Compressive Strength / Q000502:physiology*; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006620:Hip Fractures / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People; D055815:Young Adult
chemical_list: D015820:Cadherins; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human