Table 3.

Association between extreme inbreeding (EI) and multiple traits measured in UK Biobank participants (125 EI cases vs. 345,276 EI controls)

Traits (unit: trait SD)	Mean in EI cases	Mean in controls	Effect size (unit: trait SD)	Extrapolated effect size (unit: trait SD for 100% inbreeding)	Standard error (s.e.)	p Value
PEF	−0.651	0.005	−0.656	−3.88	0.099	2.8 × 10−11
Height	−0.404	0.012	−0.417	−2.46	0.090	3.2 × 10−6
HGS	−0.395	0.004	−0.441	−2.35	0.091	1.2 × 10−5
FIS	−0.570	0.010	−0.581	−3.43	0.152	1.4 × 10−4
MTCIM	−0.334	0.003	−0.337	−1.99	0.091	2.0 × 10−4
AA	−0.557	0.002	−0.559	−3.31	0.164	6.7 × 10−4
EA	−0.260	0.023	−0.283	−1.67	0.089	1.5 × 10−3
VA	0.370	0.003	−0.373	−2.21	0.179	0.037
NCh	−0.230	−0.009	−0.221	−1.31	0.089	0.013
HWR	−0.640	0.005	−0.170	−1.01	0.090	0.058
Polygenic predictor of EA*	−0.259	−0.262	4.9 × 10−4	N/A	0.018	0.978
			RR [log(RR)]		s.e. of log(RR)	P-value
NCh	1.54	1.78	0.23 [−1.46]	N/A	0.302	1.3 × 10−6
NDIS	12.2	6.90	1.44 [0.36]	N/A	0.089	3.6 × 10−5
NDIS*	13.9	8.90	1.34 [0.29]	N/A	0.083	4.4 × 10−4
NDIS parents	2.16	2.24	0.96 [−0.04]	N/A	0.065	0.507

Mean F_ROH is ~0.172 (SD: 0.067) in EI cases and ~0.003 (SD: 0.002) in EI controls. Effect sizes were estimated using either linear regression or overdispersed Poisson regression (latter for the following traits NCh, NDIS, NDIS* and NDIS parents) of the trait on the EI binary status. Extrapolated effect sizes in trait SD for 100% inbreeding were obtained by dividing estimated effect size by the difference in mean F_ROH between EI cases and EI controls, i.e., ~0.17. Traits analysed, include peak expiratory flow (PEF), standing height, handgrip strength (HGS), fluid intelligence score (FIS), mean time to correctly identify matches (MTCIM), auditory acuity (AA), number of years of education or educational attainment (EA), visual acuity (VA), number of children (NCh), hip-to-waist ratio (HWR), number of diseases diagnosed (NDIS) based on the International Classification of Diseases, Tenth Revision (ICD10). NDIS* refers to NDIS in individuals with at least one disease diagnosed. We also compared the number of disease-groups UKB participants reported their parents to be affected with (NDIS parents). RR relative risk, SD standard deviation. Estimates were adjusted for age at recruitment, recruitment centre (treated as a categorical factor), sex, year of birth (treated as a continuous variable), genotyping batch (treated as a factor), socioeconomic status measured by the Townsend deprivation index and population structure measured by ten genetic principal components estimated from HM3 SNPs. Polygenic predictor of EA was calculated using summary statistics from the Lee et al. (2018) study (excluding the UKB) and also adjusted for ten principal components. Inbreeding load for NCh was estimated as B = −log(RR) = 1.46 (95% confidence interval: [0.87–2.05]).