Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene.
Ruiz A., Heilmann S., Becker T., Hernández I., Wagner H., Thelen M., Mauleón A., Rosende-Roca M., Bellenguez C., Bis JC., Harold D., Gerrish A., Sims R., Sotolongo-Grau O., Espinosa A., Alegret M., Arrieta JL., Lacour A., Leber M., Becker J., Lafuente A., Ruiz S., Vargas L., Rodríguez O., Ortega G., Dominguez M-A., IGAP None., Mayeux R., Haines JL., Pericak-Vance MA., Farrer LA., Schellenberg GD., Chouraki V., Launer LJ., van Duijn C., Seshadri S., Antúnez C., Breteler MM., Serrano-Ríos M., Jessen F., Tárraga L., Nöthen MM., Maier W., Boada M., Ramírez A.
To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (Fundació ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P=0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio=1.31; confidence interval 95% (1.19-1.44); P=9.74 × 10(-)(9)).