The US central bank will wrap up its two-day policy meeting later in the day and is expected to indicate whether it is on track to raise interest rates.
Trading volume was also thinner with one of the region's biggest markets - Japan- closed for a public holiday.
Australia's benchmark S&P/ASX 200 ended 1.85% lower at 5,838.60 points.
Chinese shares headed lower, with Hong Kong's Hang Seng index ending 0.15% lower at 28,400.34 points, while the Shanghai Composite closed flat at 4,476.62.
In South Korea, the benchmark Kospi index closed 0.2% lower at 2,142.63.
Shares in Samsung Electronics rose 1.4% higher after its earnings came in line with the guidance it released earlier this month.
The tech giant reported a first-quarter operating profit of 6 trillion won ($5.64bn; Â£3.63bn).
Asian shares were mixed on Wednesday as investors remained cautious ahead of US growth data and the outcome of the Federal Reserve meeting.