Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians

被引：41

作者：

Luo, Yang ^{[1
,2
,3
,4
,5
]}

Suliman, Sara ^{[1
]}

Asgari, Samira ^{[1
,2
,3
,4
,5
]}

Amariuta, Tiffany ^{[1
,2
,3
,4
,5
,6
]}

Baglaenko, Yuriy ^{[1
,2
,3
,4
,5
]}

Martinez-Bonet, Marta ^{[1
]}

Ishigaki, Kazuyoshi ^{[1
,2
,3
,4
,5
]}

Gutierrez-Arcelus, Maria ^{[1
,2
,3
,4
,5
]}

Calderon, Roger ^{[7
]}

Lecca, Leonid ^{[7
]}

Lecon, Segundo R. ^{[7
]}

Jimenez, Judith ^{[7
]}

Yataco, Rosa ^{[7
]}

Contreras, Carmen ^{[7
]}

Galea, Jerome T. ^{[8
]}

Becerra, Mercedes ^{[9
,10
]}

Nejentsev, Sergey ^{[11
,12
]}

Nigrovic, Peter A. ^{[1
,13
]}

Moody, D. Branch ^{[1
]}

Murray, Megan B. ^{[9
,10
]}

Raychaudhuri, Soumya ^{[1
,2
,3
,4
,5
,14
]}

机构：

[1] Harvard Med Sch, Brigham & Womens Hosp, Div Rheumatol Inflammat & Immun, Boston, MA 02115 USA

[2] Harvard Med Sch, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

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

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

[5] Harvard Med Sch, Brigham & Womens Hosp, Ctr Data Sci, Boston, MA 02115 USA

[6] Harvard Univ, Grad Sch Arts & Sci, Cambridge, MA 02138 USA

[7] Socios Salud, Lima, Peru

[8] Univ S Florida, Sch Social Work, Tampa, FL USA

[9] Harvard Med Sch, Brigham & Womens Hosp, Dept Global Hlth & Social Med, Boston, MA 02115 USA

[10] Harvard Med Sch, Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA

[11] Univ Cambridge, Dept Med, Cambridge, England

[12] Univ Amsterdam, Med Ctr, Dept Mol Cell Biol & Immunol, Amsterdam, Netherlands

[13] Boston Childrens Hosp, Div Immunol, Boston, MA USA

[14] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Ctr Genet & Genom, Manchester, Lancs, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

欧洲研究理事会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; SUSCEPTIBILITY; VARIANTS; RISK; ELEMENTS; DETERMINANTS; ARCHITECTURE; POPULATIONS; MACROPHAGE;

D O I：

10.1038/s41467-019-11664-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Of the 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5-15% will develop active tuberculosis (TB). Approximately half will progress to active TB within the first 18 months after infection, presumably because they fail to mount an effective initial immune response. Here, in a genome-wide genetic study of early TB progression, we genotype 4002 active TB cases and their household contacts in Peru. We quantify genetic heritability (h(g)(2)) of early TB progression to be 21.2% (standard error 0.08). This suggests TB progression has a strong genetic basis, and is comparable to traits with well-established genetic bases. We identify a novel association between early TB progression and variants located in a putative enhancer region on chromosome 3q23 (rs73226617, OR = 1.18; P = 3.93 x 10(-8)). With in silico and in vitro analyses we identify rs73226617 or rs148722713 as the likely functional variant and ATP1B3 as a potential causal target gene with monocyte specific function.

引用

页数：10

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