THEORY: Yotsuba's Biological Parents Were Killed by the Irish Republican Army
DISCLAIMER: I know that theorizing about Yotsuba's origin is kind of pointless because (a) Azuma will probably never make it explicit and (b) it doesn't really matter to the story. But it can still be fun to speculate.
Now on to the theory:
Yotsuba is almost certainly a white European because people can tell that she is a foreigner on sight (Chapters 1 & 40). Koiwai presumably encountered her while traveling for his translation work and given Japan's massive commercial relationship with the Anglosphere ([Japan Exports By Country](https://tradingeconomics.com/japan/exports-by-country)), I think it's statistically likely that Koiwai is an English translator and encountered Yotsuba in an English-speaking country. We also know that Yotsuba is from an island (Chapter 14) and that her country of origin was apparently war-torn. Upon the manga's premier in 2003, Yotsuba is five years old so was presumably born around 1998.
Northern Ireland fits the bill perfectly: an English-speaking European island that was fraught with political violence until the Good Friday Accord in, wait for it...1998 ([Good Friday Agreement - Wikipedia](https://en.wikipedia.org/wiki/Good_Friday_Agreement)).
[Edit: It’s been pointed out that there is no actual evidence that a war was on in Yotsuba’s homeland; the idea arose from fan speculation. I think Azuma might have had this in mind in the early chapters, but there’s no way to know. I think the overall theory still works, but the alignment of the story with the end of The Troubles isn’t a strong datapoint.]
As a kicker, this also makes sense of Yotsuba's name and the four-leaf clover motif. After all, the shamrock is a symbol of Ireland.
I think this theory is superior to an old speculation by u/harms_away that Yotsuba is from Crimea because it accommodates the "Island" datapoint better. The only issue I see here is the floating timeline, which could mean that the manga is set whenever the run stops, but that depends on how you interpret it. Also, I don't think Yotsuba being unfamiliar with swings (Chapter 1) is relevant because she lived with Koiwai since before she could walk and talk (Chapter 107), so presumably she was raised in Japan