The effect of maternal BMI, smoking and alcohol on congenital heart diseases: a Mendelian randomisation study

Table 2 Relevance and strength of the genetic risk scores with exposures in pregnancy

Study	N participants	N SNPs in GRS	Coefficient (95% CI)^a	P-value	R²/pseudo R^{2 b}	F statistic ^c	AUC
Association of GRS for BMI with pre-/early-pregnancy BMI
ALSPAC	6253	941	0.24 (0.21, 0.26)	1 × 10⁻⁸⁰	5.6%	372	-
BiB	6196	939	0.20 (0.18, 0.23)	5 × 10⁻⁵⁹	4.1%	268	-
MoBa	45,033	868	0.25 (0.24, 0.26)	< 1 × 10⁻¹⁰⁰	6.3%	3,023	-
Association of GRS for a lifetime smoking index with any smoking during pregnancy
ALSPAC	6428	126	1.27 (1.20, 1.35)	1 × 10⁻¹⁶	1.6%	-	0.56
BiB	6482	126	1.36 (1.27, 1.45)	2 × 10⁻²⁰	2.2%	-	0.59
MoBa	41,292	119	1.27 (1.23, 1.31)	5 × 10⁻⁴⁷	1.0%	-	0.57
Association of GRS for drinks per week with any alcohol consumption in pregnancy
ALSPAC	6087	98	1.14 (1.07, 1.21)	3 × 10⁻⁵	0.4%	-	0.53
BiB	2110	99	1.08 (0.99, 1.18)	0.09	0.2%	-	0.52
MoBa	38,645	73	1.02 (0.99, 1.04)	0.17	0.007%	-	0.50
MoBa sensitivity ^d	38,645	73	1.05 (1.02, 1.08)	0.003	0.04%	-	0.51

Abbreviations: SNP Single nucleotide polymorphism, GRS Genetic risk score, CI Confidence interval, AUC Area under the curve, ALSPAC Avon Longitudinal Study of Parents and Children, BiB Born in Bradford, MoBa Norwegian Mother, Father and Child Cohort
^aEffect estimates (coefficient) are difference in mean (BMI) or odds ratio (smoking or drinking yes/no during pregnancy) per SD increase in genetic risk score
^bFor the binary outcomes (smoking and alcohol) pseudo-R² are presented
^cFor BMI F-statistic is presented; for binary outcomes (smoking and alcohol) AUC is presented
^dIn MoBa 32% consumed any alcohol during pregnancy. However, 63% of those consumed alcohol “less than once per month” based on the questionnaire data. In the sensitivity analysis shown above, we re-coded the variable so that those that consumed alcohol less than once per month were classed as non-drinkers (N.B. due to the small numbers in each individual category, we were not able to analyse these separately). This was performed as an additional check to ensure the GRS was associated with pregnancy alcohol consumption in MoBa

ISSN: 1741-7015