Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults.
BACKGROUND
As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS).


METHODS
TBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers.


RESULTS
In the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=-0.0281, β=-0.0465, respectively).


CONCLUSION
In this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture.
['Kong|Sung Hye|SH|', 'Yoon|Ji Won|JW|', 'Kim|Jung Hee|JH|', 'Park|JooYong|J|', 'Choi|Jiyeob|J|', 'Lee|Ji Hyun|JH|', 'Hong|A Ram|AR|', 'Cho|Nam H|NH|', 'Shin|Chan Soo|CS|']
D015502:Absorptiometry, Photon D000328:Adult D000368:Aged D015519:Bone Density D000071556:Cancellous Bone D015331:Cohort Studies D005260:Female D014644:Genetic Variation D055106:Genome-Wide Association Study D018398:Homeodomain Proteins D006801:Humans D057187:Independent Living D016014:Linear Models D008159:Lumbar Vertebrae D048671:MAP Kinase Kinase 5 D008297:Male D008875:Middle Aged D010024:Osteoporosis D056910:Republic of Korea D018570:Risk Assessment D014157:Transcription Factors
Genome-wide association study Cohort studies Genes, homeobox