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Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer’s disease

AuthorsDalmaso, M. Carolina; Brusco, Luís I.; Olivar, Natvidad; Muchnick, Carolina; Hanses, Claudia; Milz, Esther; Becker, Julian; Heilmann-Heimbach, Stefanie; Hoffmann, Per; Prestia, Federico A.; Galeano, Pablo; Sánchez-Avalos, M. Soledad; Martínez, Luis E.; Carulla, Mariana E.; Azurmendi Pablo J.; Liberczuk, Cynthia; Fezza, Cristina; Sampaño, Marcelo; Fierens, María; Jemar, Guillermo; Solis, Patricia; Medel, Nancy; Lisso, Julieta; Sevillano, Zulma; Bosco, Paolo; Bossú, Paola; Spalletta, Gianfranco; Galimberti, Daniela; Mancuso, Michelangelo; Nacmias, Benedetta; Sorbi, Sandro; Mecocci, Patrizia; Pilotto, Alberto; Caffarra, Paolo; Panza, Francesco; Bullido, María Jesús ; Clarimón, Jordi; Sánchez-Juan, Pascual; Coto, Eliecer; Sánchez-García, Florentino; Graff, Caroline; Ingelsson, Martin; Bellenguez, Céline; Castaño, Eduardo M.; Kairiyama, Claudia; Politis, Daniel G.; Kochen, Silvia; Scaro, Horacio; Maier, Wolfgang; Jessen, Frank; Mangone, Carlos E.; Lambert, Jean-Charles; Morelli, Laura; Ramirez, Alfredo
Issue Date2019
PublisherNature Publishing Group
CitationTranslational psychiatry 9 (2019)
AbstractRare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer’s disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.
Publisher version (URL)http://dx.doi.org/10.1038/s41398-019-0394-9
Identifiersdoi: 10.1038/s41398-019-0394-9
issn: 2158-3188
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