Genome-wide association meta-analyses to identify common genetic variants associated with XXXX in Caucasian and African Americans.

@entity1 @entity32 @entity71258 @entity571 @entity18609 @entity71256 @entity4553 @entity48223 @entity71257
OBJECTIVE: @entity4553 ( @entity4553 ) affects    36% of Caucasian adults. Although considered highly heritable, the underlying genetic determinants are unclear. We conducted the first genome-wide association study (GWAS) aimed to identify genetic variants associated with @entity4553 . METHODS: @entity4553 was assessed in three Caucasian cohorts (n=2263, n=915 and n=1231 @entity1 , respectively). In each cohort, a GWAS was conducted using 2.5   M imputed SNPs. Mixed-effect regression with the additive genetic model adjusted for age, sex, weight and within-family correlations was used for both sex-specific and combined analyses. To combine GWAS results across cohorts, fixed-effect inverse-variance meta-analyses were used. Following meta-analyses, top-associated findings were also examined in an African American cohort (n=327). RESULTS: The proportion of @entity4553 variance explained by genome-wide genotyped SNPs was 50% in @entity1 and 48% in @entity1 . A higher proportion of genetic determinants of @entity4553 were sex specific. The most significantly associated SNP in @entity1 was @entity71256 located on chr17q23-a24 near the @entity18609 gene (p=0.000000546*10(-7)); the most significantly associated SNP in @entity1 was @entity71257 located on chr13q14.1-q14.2 near the ESD gene (p=0.000000721*10(-7)). Genome-wide significant SNP-by-sex interaction was found for SNP @entity71258 located on chr11p15.1 near the @entity48223 gene (interaction p value =0.0000000041*10(-9)). The association signals diminished when combining @entity1 and @entity1 . CONCLUSIONS: The findings suggest that the potential pathophysiological mechanisms of @entity4553 are complex and strongly underlined by sex-specific interactions. The identified genetic variants imply contribution of biological pathways observed in @entity571 as well as new pathways, influencing skeletal development and @entity32 .
