The rulers of Spain had long pursued a policy of intermarriage in the hope of uniting the entire peninsular under a single sceptre. Although in 1580 these incestuous unions achieved their goal when Philip became king of Portugal. They dramatically reduced the dynasty’s gene pool. Philip’s son Don Carlos (d. 1568) and his great-grandson Carlos II (d.1700) each had only six great-grandparents instead of the normal sixteen, with an ‘inbreeding coefficient’ much the same as the incestuous offspring of siblings, of a parent and child: 0.25. Both manifested physical and mental handicaps; both died childless. In 1570 Philip married one of his nieces and they produced seven children with an ‘inbreeding coefficient of 0.22. Only one survived, Philip III, survived his father, and during his reign (1588-1621) Spain lost ground both in Europe (notably Italy) and overseas (notably in India and the Caribbean) Bankruptcy and military failure forced him to make peace with Elizabeth’s successor in 1604 and three years later to conclude a ceasefire with the Dutch Republic which in effect recognised its sovereignty.

Source: Colin Martin and Geoffrey Parker Armada: The Spanish enterprise and England’s deliverance in 1588 p481 Yale (2022)