Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores

Bond, Tom A.; Richmond, Rebecca C.; Karhunen, Ville; Cuellar-Partida, Gabriel; Borges, Maria Carolina; Zuber, Verena; Couto Alves, Alexessander; Mason, Dan; Yang, Tiffany C.; Gunter, Marc J.; Dehghan, Abbas; Tzoulaki, Ioanna; Sebert, Sylvain; Evans, David M.; Lewin, Alex M.; O’Reilly, Paul F.; Lawlor, Deborah A.; Järvelin, Marjo-Riitta

doi:10.1186/s12916-021-02216-w

Table 2 Associations of maternal BMI with outcome risk factors, and of the genetic IVs (maternal non-transmitted alleles) with maternal BMI and outcome risk factors

From: Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores

	N SNPs	R²_{maternal BMI}	Correlation with outcome risk factors^a
	N SNPs	R²_{maternal BMI}	Parental occupation	Maternal education	Paternal education	Maternal smoking	Parity	Paternal BMI	Maternal age	Paternal age
ALSPAC
N		5157	4807	4826	4572	4891	5042	3766	5157	3593
Maternal BMI^b			0.11***	− 0.12***	− 0.11***	− 0.01	0.06**	0.16***	0.00^c	− 0.01^c
Genetic IV
FTO	1	0.36%	0.03*	− 0.01	− 0.01	0.00	0.02	− 0.01	− 0.01	0.00
Speliotes	31	0.89%	0.02	0.00	− 0.03*	− 0.01	0.02	0.01	0.00	0.01
Locke	87	1.02%	0.03	− 0.01	− 0.04*	− 0.01	0.03*	0.01	0.00	0.00
Yengo	497	2.37%	0.04*	− 0.04*	− 0.05**	0.02	0.03	0.01	− 0.02	− 0.01
Lassosum	80939	6.61%	0.08***	− 0.07***	− 0.08***	0.07***	0.02	0.03*	− 0.08***	− 0.06**
BiB (SA)
N		2267	1689	2259	2258	2262	2215	475	2267	583
Maternal BMI^b			− 0.10**	− 0.08**	− 0.03	0.01	0.15***	0.12*	− 0.02^c	0.02^c
Genetic IV
FTO	1	0.77%	− 0.01	− 0.01	0.00	− 0.03	0.00	0.00	0.02	0.06
Speliotes	29	1.71%	− 0.01	0.01	0.01	− 0.04	0.00	− 0.01	0.00	− 0.05
Locke	82	1.33%	− 0.04	0.02	0.03	− 0.05*	− 0.01	− 0.06	0.00	0.02
Yengo	446	1.64%	− 0.04	− 0.04*	0.01	0.01	0.01	− 0.03	− 0.02	− 0.03
Lassosum	79101	3.46%	− 0.01	− 0.02	− 0.02	0.01	− 0.02	− 0.04	− 0.04	− 0.06
BiB (WE)
N		2000	1587	2000	1999	1999	1951	639	2000	788
Maternal BMI^b			− 0.09**	− 0.07*	0.01	0.01	0.11***	0.22***	0.00^c	0.04^c
Genetic IV
FTO	1	0.56%	0.03	0.02	− 0.01	0.00	0.00	0.03	0.00	− 0.02
Speliotes	31	0.92%	0.05	0.01	0.03	− 0.03	0.00	0.02	0.00	− 0.01
Locke	86	1.16%	0.03	0.00	0.04	− 0.01	− 0.01	0.04	− 0.02	− 0.02
Yengo	453	1.78%	− 0.01	0.00	0.05*	0.01	0.00	0.00	− 0.03	0.00
Lassosum	79101	5.21%	− 0.08*	− 0.05*	0.04	0.07*	0.04	0.03	− 0.07*	0.01

^aPearson correlation coefficients are presented here to give an indication of the direction and magnitude of associations; full regression results are presented in Additional file 1: Supplementary information S16–S19, * P < 0.05, ** P < 0.001, *** P < 1e−5. ^bAge-standardised z-scores for maternal BMI, as per the primary analyses. ^cMaternal BMI is not correlated with maternal or paternal age because it was age-standardised. SA South Asians, WE White Europeans, R² proportion of maternal BMI variance explained by the IV (maternal non-transmitted allele scores), FTO rs9939609 at the FTO locus, Speliotes, Locke, Yengo PRS calculated from SNPs that reached genome-wide significance in the BMI GWAS with the indicated first author, Lassosum PRS calculated by the lassosum method

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