Causal Relationship of Obstructive Sleep Apnea with Bone Mineral Density and the Role of BMI

Figures & data

Figure 1 Overview and analysis process of our research. Assumption 1(the relevance assumption): genetic variants are strongly related to the exposure; Assumption 2(the Independence assumption): genetic variants are independent from confounding factors of the exposure–outcome; Assumption 3 (the exclusion assumption): genetic variants influence outcomes solely through the selected exposure.

Abbreviations: MR, Mendelian randomization; GWAS, genome-wide association study; SNP, single-nucleotide polymorphism.

Table 1 Characteristics of GWAS Databases for Each Phenotype Used in Our Study

	Phenotype	Consortia	Participants (Cases/Controls)	PubMed ID
Exposures	OSA	FinnGen	16,761/201,194	33,243,845
Outcomes	TB-BMD	GWAS meta-analysis	56,284	29,304,378
	TB-BMD (age 0–15)	GWAS meta-analysis	11,807	29,304,378
	TB-BMD (age 15–30)	GWAS meta-analysis	4,180	29,304,378
	TB-BMD (age 30–45)	GWAS meta-analysis	10,062	29,304,378
	TB-BMD (age 45–60)	GWAS meta-analysis	18,805	29,304,378
	TB-BMD (age≥60)	GWAS meta-analysis	22,504	29,304,378
	LS-BMD	GEFOS	28,498	26,367,794
	FN-BMD	GEFOS	32,735	26,367,794
	FA-BMD	GWAS meta-analysis	19,705	33,097,703
	HBMD	UK Biobank	142,487	28,869,591
Mediator	BMI	GIANT	322,154	25,673,413

Abbreviations: OSA, Obstructive sleep apnea; TB-BMD, Total body bone mineral density; LS-BMD, Lumbar spine bone mineral density; FN-BMD, Femoral neck bone mineral density; FA-BMD, Forearm bone mineral density; HBMD, Heel bone mineral density; BMI, Body mass index; GWAS, genome-wide association study; FinnGen, Finnish Gene; GIANT, Genetic Investigation of Anthropometric Traits; GEFOS, Genetic Factors for Osteoporosis.

Figure 2 Mendelian randomization estimates for the associations of obstructive sleep apnea on bone mineral density.

Figure 3 Network Mendelian randomization study regarding BMI is the mediator in the associations of OSA on FA-BMD and HBMD.

Abbreviations: BMI, Body mass index; OSA, Obstructive sleep apnea; FA-BMD, Forearm bone mineral density; HBMD, Heel bone mineral density.

Figure 4 Network Mendelian randomization study regarding OSA is the mediator in the associations of BMI on FA-BMD and HBMD.

Abbreviations: BMI, Body mass index; OSA, Obstructive sleep apnea; FA-BMD, Forearm bone mineral density; HBMD, Heel bone mineral density.

Data Sharing Statement

All data are publicly available GWAS summary data. This data can be found at open GWAS (https://gwas.mrcieu.ac.uk/) and GEFOS Consortium (http://www.gefos.org/).