Both indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone mass

Table 2 The association between fetal SNP-determined birth weight and adult BMC, bone area, BMCadjArea, and BMD in UK Biobank dataset

Measurement	Sites	Outcome	63 autosomal SNPs only with fetal effect			104 autosomal SNPs			205 autosomal SNPs
Measurement	Sites	Outcome	Effect	SE	P	Effect	SE	P	Effect	SE	P
DXA	Lumbar spine (LS, N = 19,851)	BMC	0.01	0.03	0.72	0.01	0.02	0.86	0.04	0.02	0.05
		Bone area	0.15	0.03	1.26 × 10⁻⁶	0.14	0.02	1.20 × 10⁻⁸	0.17	0.02	< 2.00 × 10⁻¹⁶
		BMD	− 0.10	0.04	0.01	− 0.11	0.03	0.002	− 0.07	0.03	0.01
		BMCadjArea	− 0.19	0.05	6.03 × 10⁻⁵	− 0.20	0.04	4.80 × 10⁻⁷	− 0.16	0.03	1.04 × 10⁻⁷
	Lateral spine (LaS, N = 20,874)	BMC	− 0.07	0.03	0.03	− 0.05	0.02	0.04	− 0.02	0.02	0.19
		Bone area	0.01	0.03	0.64	0.04	0.03	0.18	0.05	0.02	0.05
		BMD	− 0.12	0.03	0.0003	− 0.11	0.03	7.54 × 10⁻⁵	− 0.07	0.02	9.00 × 10⁻⁴
		BMCadjArea	− 0.17	0.04	0.0001	− 0.18	0.03	5.81 × 10⁻⁷	− 0.14	0.02	1.86 × 10⁻⁶
QUS	Heel (N = 173,874)	Heel BMD	− 0.11	0.02	3.33 × 10⁻¹³	− 0.11	0.01	< 2.00 × 10⁻¹⁶	− 0.10	0.01	< 2.00 × 10⁻¹⁶

Exposure: weighted genetic risk scores, calculated from the 63 fetal-only effect SNPs, 104 autosomal SNPs (63 SNPs + 41 SNPs with both fetal and maternal effect), and 205 autosomal SNPs (total significant SNPs)
Outcome: BMC, bone area, BMCadjArea, and BMD. The measurements of the outcomes were standardized (z-scores) to give a mean = 0 and standard deviation = 1 to ease comparison
All analyses were adjusted for sex, age, weight, smoking, alcohol, and physical activity

ISSN: 1741-7015