  We study the large-scale anisotropy of the Universe by measuring the dipole
in the angular distribution of a flux-limited, all-sky sample of 1.36 million
quasars observed by the Wide-field Infrared Survey Explorer (WISE). This sample
is derived from the new CatWISE2020 catalog, which contains deep photometric
measurements at 3.4 and 4.6 $\mu$m from the cryogenic, post-cryogenic, and
reactivation phases of the WISE mission. While the direction of the dipole in
the quasar sky is similar to that of the cosmic microwave background (CMB), its
amplitude is over twice as large as expected, rejecting the canonical,
exclusively kinematic interpretation of the CMB dipole with a p-value of
$5\times10^{-7}$ ($4.9\sigma$ for a normal distribution, one-sided), the
highest significance achieved to date in such studies. Our results are in
conflict with the cosmological principle, a foundational assumption of the
concordance $\Lambda$CDM model.
