50% of GWAS hits for breast cancer fail to replicate

A new paper in Nature reports 65 new loci identified using genome-wide association studies in a multi-site sample of more than 100,000 subjects. Some of these loci look interesting and will likely yield some new insights into breast cancer. However, there is one sentence in this paper that I think deserves more discussion:

"Of the 102 loci that have previously been associated with breast cancer in Europeans, 49 showed evidence of association with breast cancer in the OncoArray dataset at p < 5 * 10 ^-8.

Less than half of the previous hits replicated at a genome-wide significance level. I am surprised that this paper doesn't address in any detail this significant lack of replication. Dropping the significance level to 0.05 yields a much higher replication rate.

The replicability of GWAS hits in breast cancer would make a great discussion topic for students.

risk loci