复杂疾病的风险评估：比较个人基因组检测和家族病史。

Risk estimates for complex disorders: comparing personal genome testing and family history.

作者信息

Aiyar Lila, Shuman Cheryl, Hayeems Robin, Dupuis Annie, Pu Shuye, Wodak Shoshana, Chitayat David, Velsher Lea, Davies Jill

机构信息

1] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada [2] Department of Pediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada [3] Fetal Diagnostic Center, Kapiolani Medical Center for Women and Children, Honolulu, Hawaii, USA.

出版信息

Genet Med. 2014 Mar;16(3):231-7. doi: 10.1038/gim.2013.115. Epub 2013 Sep 5.

DOI:10.1038/gim.2013.115

PMID:24009002

Abstract

PURPOSE

Personal genome testing allows the identification of single-nucleotide polymorphisms associated with an increased risk for common complex disorders. An area of concern in the use of personal genome testing is how risk estimates generated differ from traditional measures of risk (e.g., family history analysis). We sought to analyze the concordance of risk estimates generated by family history analysis and by personal genome testing.

METHODS

Risk categorizations for 20 complex conditions included in Navigenics personal genome testing were compared with risk categorization estimates derived from family history assessment using the kappa (κ) statistic.

RESULTS

The only conditions showing slight agreement between risk assessment methods were Alzheimer disease (κ = 0.131), breast cancer (κ = 0.154), and deep vein thrombosis (κ = 0.201) in females, and colon cancer (κ = 0.124) in males. Eighty-six individuals (11.4%) were found to have additional genetic risks not assessed by personal genome testing after family and medical history assessment, including 38 individuals with family histories suggestive of hereditary cancer syndromes.

CONCLUSION

Discordance between personal genome testing and family history risk estimates suggests that these methods may provide independent information that could be used in a complementary manner. Results also support that eliciting family history adds value to overall risk assessment for individuals undergoing personal genome testing.

摘要

目的

个人基因组检测能够识别与常见复杂疾病风险增加相关的单核苷酸多态性。个人基因组检测使用过程中一个令人担忧的领域是，所产生的风险估计与传统风险衡量方法（如家族史分析）有何不同。我们试图分析家族史分析和个人基因组检测所产生的风险估计的一致性。

方法

使用kappa（κ）统计量，将Navigenics个人基因组检测中包含的20种复杂疾病的风险分类与家族史评估得出的风险分类估计进行比较。

结果

风险评估方法之间仅在以下疾病上显示出轻微一致性：女性中的阿尔茨海默病（κ = 0.131）、乳腺癌（κ = 0.154）和深静脉血栓形成（κ = 0.201），以及男性中的结肠癌（κ = 0.124）。在进行家族史和病史评估后，发现86名个体（11.4%）存在个人基因组检测未评估的额外遗传风险，其中38名个体的家族史提示遗传性癌症综合征。