Genetic architecture: the shape of the genetic contribution to human traits and disease

被引：264

作者：

Timpson, Nicholas J. ^{[1
]}

Greenwood, Celia M. T. ^{[2
,3
,4
,5
]}

Soranzo, Nicole ^{[6
,7
]}

Lawson, Daniel J. ^{[1
]}

Richards, J. Brent ^{[4
,5
,8
,9
]}

机构：

[1] Univ Bristol, Sch Social & Community Med, Integrat Epidemiol Unit, MRC, Oakfield House, Bristol BS8 2BN, Avon, England

[2] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, 3755 Cote Ste Catherine, Montreal, PQ H3T 1E2, Canada

[3] McGill Univ, Dept Oncol, 3755 Cote Ste Catherine, Montreal, PQ H3T 1E2, Canada

[4] McGill Univ, Dept Human Genet & Epidemiol, 3755 Cote Ste Catherine, Montreal, PQ H3T 1E2, Canada

[5] McGill Univ, Dept Biostat & Occupat Hlth, 3755 Cote Ste Catherine, Montreal, PQ H3T 1E2, Canada

[6] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1HH, England

[7] Univ Cambridge, Dept Haematol, Long Rd, Cambridge CB2 0PT, England

[8] McGill Univ, Lady Davis Inst Med Res, Jewish Gen Hosp, Dept Med, 3755 Cote Ste Catherine, Montreal, PQ H3T 1E2, Canada

[9] Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus,Lambeth Palace Rd, London SE1 7EH, England

来源：

NATURE REVIEWS GENETICS | 2018年 / 19卷 / 02期

基金：

英国惠康基金; 加拿大自然科学与工程研究理事会; 加拿大健康研究院;

关键词：

GENOME-WIDE ASSOCIATION; DENSITY-LIPOPROTEIN CHOLESTEROL; BONE-MINERAL DENSITY; IMPAIRED GLUCOSE-TOLERANCE; RARE VARIANTS; MENDELIAN RANDOMIZATION; COMPLEX TRAITS; STATISTICAL TESTS; NATURAL-SELECTION; COMMON VARIATION;

D O I：

10.1038/nrg.2017.101

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genetic architecture describes the characteristics of genetic variation that are responsible for heritable phenotypic variability. It depends on the number of genetic variants affecting a trait, their frequencies in the population, the magnitude of their effects and their interactions with each other and the environment. Defining the genetic architecture of a complex trait or disease is central to the scientific and clinical goals of human genetics, which are to understand disease aetiology and aid in disease screening, diagnosis, prognosis and therapy. Recent technological advances have enabled genome-wide association studies and emerging next-generation sequencing studies to begin to decipher the nature of the heritable contribution to traits and disease. Here, we describe the types of genetic architecture that have been observed, how architecture can be measured and why an improved understanding of genetic architecture is central to future advances in the field.

引用

页码：110 / 124

页数：15

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