Britain’s departure from the European Union could send shock waves across the global economy and threaten more than a trillion dollars in investment and trade with the United States. International policymakers are ramping up their warnings of the dangers of a British exit – popularly known as “Brexit” – from the political and economic alliance that has united Europe for the past four decades. Voters in Britain will decide whether to leave or remain in the European Union in a referendum on Thursday, but financial market volatility has already spiked as polls show a growing desire to abandon the partnership. The decision carries hefty consequences for American businesses, which employ more than a million people in Britain. The United States is the largest single investor in Britain, and many firms consider it the gateway to free trade with the 28 nations that make up the E.U. A Brexit would jeopardize their access to those markets, potentially reducing revenue and forcing some firms to consider relocating their European operations elsewhere. That has put corporate America onto the front lines of the campaign to keep the union together, with several of Wall Street’s biggest names donating substantial sums to the effort. A Brexit would be “bad for the U.K., it would be bad for Europe, it would be bad for the world, including the United States,” Angel Gurría, secretary general of the Organization for Economic Cooperation and Development, said in an interview. “You already have enough uncertainty in the world today. We don’t need more.” The International Monetary Fund on Friday issued one of the most dire forecasts to date, calling the impact of Britain’s departure from the European Union “negative and substantial.” The fund predicted that a Brexit could reduce economic growth by up to 5.6 percent over the next three years in its worst-case scenario. The gloomy outlook is driven by an expected sharp decline in the pound and severe disruptions in trade as the nation is forced to renegotiate deals with countries across the continent, potentially on worse terms. Those concerns were echoed by policymakers around the world last week. The Bank of England called the referendum the “largest immediate risk facing U.K. financial markets, and possibly also global financial markets.” Finland’s finance minister dubbed Brexit a “Lehman Brothers moment,” referring to the collapse of the U.S. investment bank during the depths of the financial crisis in 2008. And in Washington, Federal Reserve Board Chair Janet L. Yellen said the threat of a Brexit factored into its decision to remain cautious and keep its benchmark interest rate unchanged last week. “They basically all say somewhat of the same thing,” said Jacob Kirkegaard, senior fellow at the Peterson Institute for International Economics. “Namely, that there is little doubt that the economics will be bad.” Financial markets are already starting to feel the tremors. Britain’s currency has fluctuated wildly, while London’s major stock index plunged nearly 6 percent in less than two weeks and flirted with its lowest level in four months. Skittish investors piled into the safe haven of government debt, and high demand pushed yields on the 10-year German bond into negative territory last week for the first time in history. In the United States, yields on comparable Treasury notes dropped to near-record lows not seen since 2012. The challenges are coming at an already weak moment for Europe’s economy – and the world’s. Europe is still recovering from the series of financial crises that have been roiling countries such as Greece and Italy along with others across the continent. Waves of refugees from the Middle East are spurring political and cultural unrest. And there are worries about the strength of the economies of Europe’s major trading partners, including China and the United States. While financial markets would bear the brunt of the immediate impact of a Brexit, the referendum raises deeper questions for businesses on both sides of the Atlantic. If Britain votes to leave, it would spend at least two years working out the terms of its departure, with all signs pointing to an acrimonious negotiation. Britain would also need to procure trade agreements with countries around the world, including the United States, a process that could take years. Businesses say the protracted debate would leave them stuck in limbo. “Nobody knows at this point how the world would look like with the U.K. out of the E.U.,” said Emanuel Adam, head of policy and trade for BritishAmerican Business, which represents companies in New York and London. “This alone creates an uncertainty that businesses don’t wish to see.” The United States exported $56 billion worth of goods to Britain last year, but that number is dwarfed by the $588 billion in U.S. investment there, in sectors ranging from banking to manufacturing to real estate. Likewise, Britain has plowed nearly half a trillion dollars into the United States and employs more than a million workers here. Those deep ties mean that trouble on one side of the Atlantic easily can migrate to the other shore.