Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood

被引：470

作者：

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

Chaffin, Mark ^{[3
]}

Wade, Kaitlin H. ^{[5
,6
,7
]}

Zahid, Sohail ^{[3
,4
]}

Brancale, Joseph ^{[4
,8
]}

Xia, Rui ^{[9
]}

Distefano, Marina ^{[10
,11
,12
]}

Senol-Cosar, Ozlem ^{[10
,11
,12
]}

Haas, Mary E. ^{[3
]}

Bick, Alexander ^{[1
,3
,4
]}

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

Lander, Eric S. ^{[3
,13
,14
]}

Smith, George Davey ^{[5
,6
]}

Mason-Suares, Heather ^{[10
,11
,12
]}

Fornage, Myriam ^{[9
]}

Lebo, Matthew ^{[10
,11
,12
]}

Timpson, Nicholas J. ^{[5
,6
,7
]}

Kaplan, Lee M. ^{[4
,8
]}

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

机构：

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

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

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

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

[5] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England

[6] Univ Bristol Sch Med, Populat Hlth Sci, Bristol BS8 1TH, Avon, England

[7] Avon Longitudinal Study Parents & Children, Bristol BS8 1TH, Avon, England

[8] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA

[9] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA

[10] Partners HealthCare Personalized Med, Lab Mol Med, Cambridge, MA 02139 USA

[11] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[12] Harvard Med Sch, Dept Pathol, Cambridge, MA 02115 USA

[13] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[14] Harvard Med Sch, Program Hlth Sci & Technol, Boston, MA 02115 USA

来源：

CELL | 2019年 / 177卷 / 03期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

MISSING HERITABILITY; RISK PREDICTION; FRAMESHIFT MUTATION; GENETIC-VARIATION; BODY-WEIGHT; VARIANTS; PREVALENCE; DEFICIENCY; PREVENTION; CHILDHOOD;

D O I：

10.1016/j.cell.2019.03.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal differences in birth weight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by 18 years of age. This new approach to quantify inherited susceptibility to obesity affords new opportunities for clinical prevention and mechanistic assessment.

引用

页码：587 / +

页数：19

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