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

• Published in: Bone (New York, N.Y.) Vol. 51; no. 6; pp. 1000 - 1007
• Main Authors: Han, Yingying, Pei, Yufang, Liu, Yaozhong, Zhang, Lei, Wu, Shuyan, Tian, Qing, Chen, Xiangding, Shen, Hui, Zhu, Xuezhen, Papasian, Christopher J., Deng, Hongwen
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.12.2012; Elsevier
• Subjects: Adult; Appendicular lean mass; Asian Continental Ancestry Group; Biological and medical sciences; Bivariate GWAS; Bone turnover; Cadherin; Cadherins - genetics; Compressive Strength - physiology; Compressive strength index; DCHS2; desaturase; European Continental Ancestry Group; FADSs; Fatty Acid Desaturases - genetics; Fatty acids; Fractures; Fundamental and applied biological sciences. Psychology; Genome-Wide Association Study - methods; Genomes; Genotyping; Hip; Hip Fractures - genetics; Humans; Limbs; Male; Male-specific; Middle Aged; Orthopedics; Osteoporosis; Polymorphism, Single Nucleotide - genetics; Replication; Risk assessment; Single-nucleotide polymorphism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Young Adult; FADSs; DCHS2; Male-specific; Appendicular lean mass; Bivariate GWAS; Compressive strength index; Morphology; Male; Compressive strength; Genome; Fatty acids
• DOI: 10.1016/j.bone.2012.08.127
• ISSN: 8756-3282; 1873-2763

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. ► Five SNPs in FADS1/FADS2 and DCHS2 were identified in males. ► The identified SNPs were bivariately related with CSI and ALM. ► The saturated state of fatty acids may be related with elder osteoporosis.