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Meta-Analysis
. 2019 Jan 31;9(1):55.
doi: 10.1038/s41398-019-0394-9.

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

Maria Carolina Dalmasso  1 , Luis Ignacio Brusco  2   3   4 , Natividad Olivar  2   3 , Carolina Muchnik  5 , Claudia Hanses  6 , Esther Milz  7 , Julian Becker  6 , Stefanie Heilmann-Heimbach  8   9 , Per Hoffmann  8   9   10 , Federico A Prestia  1 , Pablo Galeano  1 , Mariana Soledad Sanchez Avalos  11 , Luis Eduardo Martinez  4 , Mariana Estela Carulla  4 , Pablo Javier Azurmendi  5 , Cynthia Liberczuk  2 , Cristina Fezza  5 , Marcelo Sampaño  2 , Maria Fierens  2 , Guillermo Jemar  2 , Patricia Solis  12 , Nancy Medel  12 , Julieta Lisso  12 , Zulma Sevillano  12 , Paolo Bosco  13 , Paola Bossù  14 , Gianfranco Spalletta  15 , Daniela Galimberti  16 , Michelangelo Mancuso  17 , Benedetta Nacmias  18 , Sandro Sorbi  18   19 , Patrizia Mecocci  20 , Alberto Pilotto  21 , Paolo Caffarra  22   23 , Francesco Panza  24 , Maria Bullido  25   26   27 , Jordi Clarimon  26   28 , Pascual Sánchez-Juan  29 , Eliecer Coto  30 , Florentino Sanchez-Garcia  31 , Caroline Graff  32   33 , Martin Ingelsson  34 , Céline Bellenguez  35   36   37 , Eduardo Miguel Castaño  1 , Claudia Kairiyama  4 , Daniel Gustavo Politis  4 , Silvia Kochen  12 , Horacio Scaro  11 , Wolfgang Maier  38   39 , Frank Jessen  38   40 , Carlos Alberto Mangone  2 , Jean-Charles Lambert  35   36   37 , Laura Morelli  41 , Alfredo Ramirez  42   43
Affiliations
Meta-Analysis

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

Maria Carolina Dalmasso et al. Transl Psychiatry. .

Abstract

Rare 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.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

All participants had agreed by signed informed consent to participate in genetic studies approved by our Institutional Review Board.

Figures

Fig. 1
Fig. 1. Ancestry analysis of DNA samples that passed quality controls.
a Distribution of genetic ancestry in Alzheimer’s disease (AD) cases and controls. Bar-plots represent each participant on the x-axis, and his percent of European (CEU), African (AFR), and Native American (NAM) ancestry on the y-axis. b Ancestry of rare variant carriers. Box-plots show ancestry composition in percent of people carrying TREM2 p.R47H (n = 3), TREM2 p.R62H (n = 16), PLCG2 p.P522R (n = 6), and ABI3 p.S209F (n = 11) mutations
Fig. 2
Fig. 2. Ancestry of chromosomes containing the rare variants.
Principal component analysis (PCA) of ancestry results for a chromosome 6, containing TREM2 p.R47H (black) and TREM2 p.R62H (gray); b chromosome 16, containing PLCG2 p.P522R (black); and c chromosome 17, containing ABI3 p.S209F. Ancestral populations are European (blue), African (red), and Native American (green). Percent of distribution explained by each principal component (PC) it is shown in parenthesis
See this image and copyright information in PMC

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