Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations

被引：1933

作者：

Khera, Amit V. ^{[1
,2
,3
,4
,5
]}

Chaffin, Mark ^{[5
]}

Aragam, Krishna G. ^{[1
,2
,3
,4
,5
]}

Haas, Mary E. ^{[5
]}

Roselli, Carolina ^{[5
]}

Choi, Seung Hoan ^{[5
]}

Natarajan, Pradeep ^{[2
,3
,4
,5
]}

Lander, Eric S. ^{[5
]}

Lubitz, Steven A. ^{[4
,5
]}

Ellinor, Patrick T. ^{[4
,5
]}

Kathiresan, Sekar ^{[1
,2
,3
,4
,5
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Cardiol Div, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA

[4] Harvard Med Sch, Boston, MA 02115 USA

[5] Broad Inst Harvard & MIT, Cardiovasc Dis Initiat, Cambridge, MA 02142 USA

来源：

NATURE GENETICS | 2018年 / 50卷 / 09期

基金：

美国国家卫生研究院;

关键词：

CORONARY-HEART-DISEASE; GENETIC RISK; ASSOCIATION; PREDICTION; RARE; PREVENTION; LOCI;

D O I：

10.1038/s41588-018-0183-z

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation(1). Proposed clinical applications have largely focused on finding carriers of rare monogenic mutations at several-fold increased risk. Although most disease risk is polygenic in nature(2-5), it has not yet been possible to use polygenic predictors to identify individuals at risk comparable to monogenic mutations. Here, we develop and validate genome-wide polygenic scores for five common diseases. The approach identifies 8.0, 6.1, 3.5, 3.2, and 1.5% of the population at greater than threefold increased risk for coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel disease, and breast cancer, respectively. For coronary artery disease, this prevalence is 20-fold higher than the carrier frequency of rare monogenic mutations conferring comparable risk(6). We propose that it is time to contemplate the inclusion of polygenic risk prediction in clinical care, and discuss relevant issues.

引用

页码：1219 / +

页数：7

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