Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease
Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease
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DOI：
10.1038/s41398-019-0394-9
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发表时间：
2019-01-31
影响因子：
6.8
通讯作者：
Ramirez, Alfredo
中科院分区：
文献类型：
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作者：
Carolina Dalmasso, Maria;Ignacio Brusco, Luis;Ramirez, Alfredo
TREM2、PLCG2 和 ABI3 中的罕见编码变异最近与白种人阿尔茨海默病 (AD) 的易感性相关。变异的频率和与 AD 相关的影响因种族而异。为了开始填补南美洲 AD 遗传学的空白并评估这些变异对不同种族的影响，我们研究了阿根廷人群中与血统相关的这些变异。在 419 例 AD 病例和 486 例对照中对 TREM2（rs143332484 和 rs75932628）、PLCG2（rs72824905）和 ABI3（rs616338）进行了基因分型。对欧洲人群进行了荟萃分析。祖先是根据全基因组基因分型结果估计的。所有变体都显示出与之前报道的类似的频率和比值比。通过荟萃分析，它们与 AD 的关联达到了统计学显着性。尽管阿根廷人是混血儿，但变异携带者主要是白人血统。 TREM2、PLCG2 和 ABI3 中的罕见编码变异也调节阿根廷人群对 AD 的易感性，并且他们可能具有欧洲遗产。
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.