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Background Pony #4683
And I felt like they are relatable to one Soul Eater ship, Twilight is Maka, and Spike is Soul, Twispike can be Maka x Soul but in MLP:FiM.
Background Pony #4683
@Background Pony #D516  
Discord WAS also (S4), but he claimed Fluttershy and acted yandere over her (S5 onwards).  
Big Macintosh got owned by Starlight’s baker.  
Don’t forget Shining Armor… Nope…  
King Sombra is ded.
Background Pony #84EB
Twispike is the best straight ship involving Twilight of all, also around the top 5 of Spike’s heterosexual ships.
Background Pony Number 17
My Little Pony - 1992 Edition

They are related. Twilight hatched him, after all. And he grew up in her family as a sibling, even if half the time she treated him as her pet rather than her little brother.
It may not be a blood relation, but if MLP:FIM’s shown us anything, it’s that relationships based on friendship/love are just as valid as those based on bloodline.