Molecular
Transgenerational impact of obesity-associated genotypes on early life proteomics Jian Huang* Jian Huang Jinyi Che Michelle Z.L. Kee Dennis Wang
Parental non-transmitted alleles yield an indirect transgenerational impact. Early-life proteomics elucidates the mechanisms underlying developmental processes including obesity. Considering the gene-environment interplay, we investigated the influence of parental non-transmitted obesity-associated genotype on early-life proteomics in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort.
Haplotypes were estimated by accounting for trio information using SHAPEIT v2. Parental non-transmitted alleles for 706 trios were inferred from a local long-range (+/- 500kb) haplotype. Parental non-transmitted and child polygenic risk scores (PRS) were constructed using a trans-ancestry method (PRS-CSx) incorporating both European and East Asian GWAS of body mass index. Plasma neurology-related and inflammation proteins were measured at ~8 years (N=528). We used multiple linear regression, accounting for multiple comparisons of 2 parental PRS, 182 proteins and 3 child sex groups (boys, girls, and both).
Paternal non-transmitted PRS was inversely associated with MSR1 and SIGLEC1 in boys (MSR1: beta=-0.45, 95% CI [-0.60,-0.32], p=1.5*10-9; SIGLEC1: -0.38, [-0.52, -0.24], 4.6*10-7). Both proteins are relevant to immune response. These associations were sustained after adjusting for child PRS for obesity. No associations were observed for maternal non-transmitted PRS.
Our findings suggest paternal non-transmitted obesity-associated genotype influences offspring’s early-life proteomics, indicating the role of paternal factors in children’s development.