@menelion @technocounselor I asked this to Truthly, an AI grounded in Catholic teaching, and here is a part of its response.
What About the Genetics?
Here is where the question gets especially interesting. The concern about genetic deformities from close-relative reproduction is real — but it is real today because of the accumulation of genetic mutations over thousands of generations.
Inbreeding depression — the reduced fitness of offspring from mating between close relatives — is in general mainly caused by the unmasking of recessive deleterious alleles in homozygous genotypes. In other words, harmful traits emerge when two copies of a damaged gene are inherited from both parents. But that can only happen if those damaged genes already exist in the gene pool.
Mutations accumulate and increase the frequency of potentially lethal genes in the human gene pool — the "genetic load" — and mutations will continue to accumulate until a new equilibrium is reached.
Here is the key insight: at the beginning of humanity, genetic mutations had barely begun to accumulate. Adam and Eve, created by God in a state of original integrity, would have had near-perfect genetic material. Their children, being only one generation removed from this original purity, would have carried very few harmful recessive mutations. With so few defective genes in the pool, the risk of two siblings passing on matching harmful recessives to their children was extraordinarily low — essentially negligible.
As generations passed and mutations slowly accumulated across the human population, the risk of harmful genetic expression through close-relative unions grew proportionally. This is precisely why God, in His providence, later forbade such unions — not because they were always wrong, but because they became increasingly dangerous and socially disordering.