Parental disease and over transmission of genetic risk for diabetes are related to Congenital Heart Disease in offspring



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Catherine Tcheandjieu DVM PhD, John Gorzynski DVM, Aldo Cordova Palomera, Priyanka Saha BS, Jane W. Newburger, Christine E. Seidman, Wendy K. Chung, Elizabeth Goldmuntz, Martina Brueckner, George A. Porter, Jr., Richard W. Kim, Deepak Srivastava, Martin Tristani-Firouzi, Bruce D. Gelb, and James Priest MD

Maternal diabetes and elevated blood glucose during pregnancy are the most recognized risk factor for Congenital heart disease (CHD). However, the contribution or relationship to other maternal conditions such as cancer, lung, and neurological diseases, in addition to any paternal contribution to CHD risk in offspring are largely unexplored. The relationship of parental conditions was assessed using the 500,000 participants of the UK-biobank among which, 2006 adults have CHD. in the UK-biobank, a survey uniformly ascertained the Self-reported parental history of diseases (including diabetes, heart disease (unspecified), chronic bronchitis, cancer, Parkinson and Alzheimer disease, and severe depression) at the time of enrollment.

In a separate study of 850 trios (2550 individuals) with array genotyping data from the Pediatric Cardiology Genomic Consortium (PCGC), the deviation in the transmission of the genetic risk from parent to child for each condition was tested using the transmission disequilibrium test based on the Polygenic risk score (pTDT). In the UK Biobank CHD risk was associated with history of heart diseases in both parents [OR=1.41(1.19–1.66), p=5x10-05], chronic bronchitis/emphysema in mother or father [OR=1.22(1.07–1.39), p=2.8x1003], and Alzheimer in mother [OR=1.26(1.08 – 1.47), p=2.2x10-03] but not with the parental history for diabetes. Among the trios, we found a deviation in the transmission of PRS from parent to child for diabetes [mean(pTDT)=0.15(0.05–0.25) p=3x10-03], chronic obstructive pulmonary diseases (COPD) [mean(pTDT)=0.13(0.02–0.24) p =0.02], and Alzheimer disease [mean(pTDT)=0.11(0.06 – 0.16), p=0.02]. Our findings suggest that lifetime risk of heart, lung

and Alzheimer diseases in the parents may be related to the risk of CHD in offspring. Additionally, risk alleles for diabetes, COPD, and Alzheimer in the parents were observed to be over-transmitted from parent to child, suggesting that these novel inherited risk alleles for CHD may not be limited to a maternal or in utero metabolic effect.

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