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The West Virginia Democrat said in a statement: “Her overtly partisan statements will have a toxic and detrimental impact on the important working relationship between members of Congress and the next director of the Office of Management & Budget. For this reason, I cannot support her nomination.”
With the Senate split 50:50, his opposition could sink Ms Tanden’s nomination.
Mr Manchin says he carefully reviewed Ms Tanden’s public statement and tweets “that were so personally directed towards my colleagues on both sides of the aisle”.
The senator adds: “As I have said before, we must take meaningful steps to end the political division and dysfunction that pervades our politics. At a time of grave crisis, it is more important than ever that we chart a new bipartisan course that helps address the many serious challenges facing our nation.”
Ms Tanden was confronted with her past tweets about Republicans and the progressive wing of the Democratic Party during her confirmation hearings.
Appearing before the Senate Budget Committee she faced Mr Sanders, Independent Senator for Vermont, with whom she has previously sparred.
While the pair have shared political goals, and Mr Sanders has said that he would support her nomination, they have a contentious relationship dating back to her support for Hillary Clinton, his challenger for the Democratic nomination in 2016.
In her opening statement to the committee, Ms Tanden said she regretted some of her past social media posts.
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