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通过协偏度分析该区域阿尔茨海默病风险的单倍型结构。

Haplotype architecture of the Alzheimer's risk in the region via co-skewness.

作者信息

Kulminski Alexander M, Philipp Ian, Loika Yury, He Liang, Culminskaya Irina

机构信息

Biodemography of Aging Research Unit Social Science Research Institute Duke University Durham North Carolina USA.

出版信息

Alzheimers Dement (Amst). 2020 Nov 11;12(1):e12129. doi: 10.1002/dad2.12129. eCollection 2020.

DOI:10.1002/dad2.12129
PMID:33204816
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7656174/
Abstract

INTRODUCTION

As a multifactorial polygenic disorder, Alzheimer's disease (AD) can be associated with complex haplotypes or compound genotypes.

METHODS

We examined associations of 4960 single nucleotide polymorphism (SNP) triples, comprising 32 SNPs from five genes in the apolipoprotein E gene () region with AD in a sample of 2789 AD-affected and 16,334 unaffected subjects.

RESULTS

We identified a large number of 1127 AD-associated triples, comprising SNPs from all five genes, in support of definitive roles of complex haplotypes in predisposition to AD. These haplotypes may not include the ε4 and ε2 alleles. For triples with rs429358 or rs7412, which encode these alleles, AD is characterized mainly by strengthening connections of the ε4 allele and weakening connections of the ε2 allele with the other alleles in this region.

DISCUSSION

Dissecting heterogeneity attributed to AD-associated complex haplotypes in the region will target more homogeneous polygenic profiles of people at high risk of AD.

摘要

引言

作为一种多因素多基因疾病，阿尔茨海默病（AD）可能与复杂单倍型或复合基因型相关。

方法

我们在2789名AD患者和16334名未受影响的受试者样本中，研究了4960个单核苷酸多态性（SNP）三联体的关联性，这些三联体包含载脂蛋白E基因（）区域五个基因中的32个SNP与AD的关系。

结果

我们鉴定出大量1127个与AD相关的三联体，包含来自所有五个基因的SNP，这支持了复杂单倍型在AD易感性中起决定性作用。这些单倍型可能不包括ε4和ε2等位基因。对于编码这些等位基因的rs429358或rs7412的三联体，AD的主要特征是该区域中ε4等位基因的连接增强，而ε2等位基因与其他等位基因的连接减弱。

讨论

剖析该区域中与AD相关的复杂单倍型所导致的异质性，将针对AD高风险人群更具同质性的多基因特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fdc/7656174/e20bea950bd8/DAD2-12-e12129-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fdc/7656174/1adadcacb38a/DAD2-12-e12129-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fdc/7656174/fdbb00108fb9/DAD2-12-e12129-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fdc/7656174/e20bea950bd8/DAD2-12-e12129-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fdc/7656174/1adadcacb38a/DAD2-12-e12129-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fdc/7656174/fdbb00108fb9/DAD2-12-e12129-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fdc/7656174/e20bea950bd8/DAD2-12-e12129-g002.jpg

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