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

Table 3 The association between maternal SNP-determined birth weight and offspring BMD in the UK Biobank dataset

Analysis sample	Outcome	Exposure	31 autosomal SNPs only with maternal effect			72 autosomal SNPs			205 autosomal SNPs
Analysis sample	Outcome	Exposure	Effect	SE	P	Effect	SE	P	Effect	SE	P
Mother-offspring pairs (N = 4,284)	Offspring heel BMD	Maternal GRS	− 0.001	0.0006	0.03	− 0.001	0.0003	0.01	− 0.001	0.0002	0.002
	Offspring heel BMD	Maternal GRS—adjusted for offspring GRS	− 0.001	0.0007	0.04	− 0.001	0.0004	0.01	− 0.001	0.0002	0.009
	Offspring birth weight	Maternal GRS	0.01	0.003	5.07×10⁻⁷	0.01	0.001	1.40×10⁻⁹	0.007	0.001	8.76×10⁻¹²
	Offspring birth weight	Maternal GRS—adjusted for offspring GRS	0.01	0.003	0.0003	0.007	0.002	0.0002	0.003	0.001	0.008
Father-offspring pairs (N = 1,935)	Offspring heel BMD	Paternal GRS	0.0003	0.001	0.76	0.0003	0.0006	0.63	− 0.0003	0.0003	0.41
	Offspring heel BMD	Paternal GRS—adjusted for offspring GRS	− 0.000002	0.001	0.98	0.00001	0.0007	0.99	− 0.0003	0.0004	0.36
	Offspring birth weight	Paternal GRS	− 0.001	0.004	0.76	0.001	0.002	0.64	0.002	0.001	0.19
	Offspring birth weight	Paternal GRS—adjusted for offspring GRS	− 0.008	0.005	0.09	− 0.005	0.003	0.08	− 0.002	0.002	0.20

The regression coefficients give the estimated expected change in offspring eBMD (g/cm²), per one unit (i.e., allele) increase in maternal/paternal genetic risk score (calculated from the 31 maternal-only effect SNPs, 72 autosomal SNPs with both fetal and maternal effect and 205 total significant autosomal SNPs), with or without conditioning on offspring genetic risk score
The linear mixed-effects model was applied. All analyses were adjusted for offspring age, sex, weight, and assessment center

ISSN: 1741-7015