Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma

被引：54

作者：

Igartua, Catherine ^{[1
]}

Myers, Rachel A. ^{[1
]}

Mathias, Rasika A. ^{[2
]}

Pino-Yanes, Maria ^{[3
,4
]}

Eng, Celeste ^{[3
]}

Graves, Penelope E. ^{[5
,6
]}

Levin, Albert M. ^{[7
]}

Del-Rio-Navarro, Blanca E. ^{[8
]}

Jackson, Daniel J. ^{[9
]}

Livne, Oren E. ^{[1
]}

Rafaels, Nicholas ^{[10
]}

Edlund, Christopher K. ^{[11
]}

Yang, James J. ^{[12
]}

Huntsman, Scott ^{[3
]}

Salam, Muhammad T. ^{[11
]}

Romieu, Isabelle ^{[13
]}

Mourad, Raphael ^{[1
]}

Gern, James E. ^{[9
,14
]}

Lemanske, Robert F. ^{[9
,15
]}

Wyss, Annah ^{[16
]}

Hoppin, Jane A. ^{[16
,17
]}

Barnes, Kathleen C. ^{[2
]}

Burchard, Esteban G. ^{[3
,18
]}

Gauderman, W. James ^{[11
]}

Martinez, Fernando D. ^{[5
,6
]}

Raby, Benjamin A. ^{[19
,20
]}

Weiss, Scott T. ^{[19
]}

Williams, L. Keoki ^{[21
,22
]}

London, Stephanie J. ^{[16
]}

Gilliland, Frank D. ^{[11
]}

Nicolae, Dan L. ^{[1
,23
,24
]}

Ober, Carole ^{[1
]}

机构：

[1] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[2] Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA

[3] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[4] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid 28029, Spain

[5] Univ Arizona, Arizona Resp Ctr, Tucson, AZ 85721 USA

[6] Univ Arizona, Inst BIO5, Tucson, AZ 85721 USA

[7] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI 48202 USA

[8] Hosp Infantil Mexico Dr Federico Gomez, Mexico City 06720, DF, Mexico

[9] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53726 USA

[10] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21224 USA

[11] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[12] Univ Michigan, Sch Nursing, Ann Arbor, MI 48202 USA

[13] Int Agcy Res Canc, F-69372 Lyon, France

[14] Univ Wisconsin, Sch Med & Publ Hlth, Dept Internal Med, Madison, WI 53726 USA

[15] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53726 USA

[16] NIEHS, Div Intramural Res, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA

[17] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27607 USA

[18] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA

[19] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA USA

[20] Harvard Univ, Sch Med, Div Pulm & Crit Care Med, Boston, MA USA

[21] Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI 48202 USA

[22] Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI 48202 USA

[23] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[24] Univ Chicago, Dept Stat, Chicago, IL 60637 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; MTHFR C677T POLYMORPHISM; MISSING HERITABILITY; LOCI; EXPRESSION; RISK; METAANALYSIS; FAMILY; PREGNANCY; GENETICS;

D O I：

10.1038/ncomms6965

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：

Common variants at many loci have been robustly associated with asthma but explain little of the overall genetic risk. Here we investigate the role of rare (<1%) and low-frequency (1-5%) variants using the Illumina HumanExome BeadChip array in 4,794 asthma cases, 4,707 non-asthmatic controls and 590 case-parent trios representing European Americans, African Americans/African Caribbeans and Latinos. Our study reveals one low-frequency missense mutation in the GRASP gene that is associated with asthma in the Latino sample (P = 4.31 x 10(-6); OR = 1.25; MAF = 1.21%) and two genes harbouring functional variants that are associated with asthma in a gene-based analysis: GSDMB at the 17q12-21 asthma locus in the Latino and combined samples (P = 7.81 x 10(-8) and 4.09 x 10(-8), respectively) and MTHFR in the African ancestry sample (P = 1.72 x 10(-6)). Our results suggest that associations with rare and low-frequency variants are ethnic specific and not likely to explain a significant proportion of the 'missing heritability' of asthma.

引用

页数：8

共 46 条

[1] A method and server for predicting damaging missense mutations
Adzhubei, Ivan A.
Schmidt, Steffen
Peshkin, Leonid
Ramensky, Vasily E.
Gerasimova, Anna
Bork, Peer
Kondrashov, Alexey S.
Sunyaev, Shamil R.
[J]. NATURE METHODS, 2010, 7 (04) : 248 - 249
[2] The agricultural health study
Alavanja, MCR
Sandler, DP
McMaster, SB
Zahm, SH
McDonnell, CJ
Lynch, CF
Pennybacker, M
Rothman, N
Dosemeci, M
Bond, AE
Blair, A
[J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 1996, 104 (04) : 362 - 369
[3] A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations
Bonnelykke, Klaus
Sleiman, Patrick
Nielsen, Kasper
Kreiner-Moller, Eskil
Mercader, Josep M.
Belgrave, Danielle
den Dekker, Herman T.
Husby, Anders
Sevelsted, Astrid
Faura-Tellez, Grissel
Mortensen, Li Juel
Paternoster, Lavinia
Flaaten, Richard
Molgaard, Anne
Smart, David E.
Thomsen, Philip F.
Rasmussen, Morten A.
Bonas-Guarch, Silvia
Holst, Claus
Nohr, Ellen A.
Yadav, Rachita
March, Michael E.
Blicher, Thomas
Lackie, Peter M.
Jaddoe, Vincent W. V.
Simpson, Angela
Holloway, John W.
Duijts, Liesbeth
Custovic, Adnan
Davies, Donna E.
Torrents, David
Gupta, Ramneek
Hollegaard, Mads V.
Hougaard, David M.
Hakonarson, Hakon
Bisgaard, Hans
[J]. NATURE GENETICS, 2014, 46 (01) : 51 - +
[4] Rhinovirus Wheezing Illness and Genetic Risk of Childhood-Onset Asthma
Caliskan, Minal
Bochkov, Yury A.
Kreiner-Moller, Eskil
Bonnelykke, Klaus
Stein, Michelle M.
Du, Gaixin
Bisgaard, Hans
Jackson, Daniel J.
Gern, James E.
Lemanske, Robert F., Jr.
Nicolae, Dan L.
Ober, Carole
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (15) : 1398 - 1407
[5] Uncovering the roles of rare variants in common disease through whole-genome sequencing
Cirulli, Elizabeth T.
Goldstein, David B.
[J]. NATURE REVIEWS GENETICS, 2010, 11 (06) : 415 - 425
[6] Whole-exome sequencing of a pedigree segregating asthma
DeWan, Andrew T.
Egan, Kathryn Brigham
Hellenbrand, Karen
Sorrentino, Keli
Pizzoferrato, Nicole
Walsh, Kyle M.
Bracken, Michael B.
[J]. BMC MEDICAL GENETICS, 2012, 13
[7] GENETICS OF ASTHMA AND HAY-FEVER IN AUSTRALIAN TWINS
DUFFY, DL
MARTIN, NG
BATTISTUTTA, D
HOPPER, JL
MATHEWS, JD
[J]. AMERICAN REVIEW OF RESPIRATORY DISEASE, 1990, 142 (06): : 1351 - 1358
[8] Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: The Genes-environments & Admixture in Latino Americans study
Galanter, Joshua M.
Gignoux, Christopher R.
Torgerson, Dara G.
Roth, Lindsey A.
Eng, Celeste
Oh, Sam S.
Nguyen, Elizabeth A.
Drake, Katherine A.
Huntsman, Scott
Hu, Donglei
Sen, Saunak
Davis, Adam
Farber, Harold J.
Avila, Pedro C.
Brigino-Buenaventura, Emerita
LeNoir, Michael A.
Meade, Kelley
Serebrisky, Denise
Borrell, Luisa N.
Rodriguez-Cintron, William
Estrada, Andres Moreno
Mendoza, Karla Sandoval
Winkler, Cheryl A.
Klitz, William
Romieu, Isabelle
London, Stephanie J.
Gilliland, Frank
Martinez, Fernando
Bustamante, Carlos
Williams, L. Keoki
Kumar, Rajesh
Rodriguez-Santana, Jose R.
Burchard, Esteban G.
[J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2014, 134 (02) : 295 - 305
[9] The International HapMap Project
Gibbs, RA
Belmont, JW
Hardenbol, P
Willis, TD
Yu, FL
Yang, HM
Ch'ang, LY
Huang, W
Liu, B
Shen, Y
Tam, PKH
Tsui, LC
Waye, MMY
Wong, JTF
Zeng, CQ
Zhang, QR
Chee, MS
Galver, LM
Kruglyak, S
Murray, SS
Oliphant, AR
Montpetit, A
Hudson, TJ
Chagnon, F
Ferretti, V
Leboeuf, M
Phillips, MS
Verner, A
Kwok, PY
Duan, SH
Lind, DL
Miller, RD
Rice, JP
Saccone, NL
Taillon-Miller, P
Xiao, M
Nakamura, Y
Sekine, A
Sorimachi, K
Tanaka, T
Tanaka, Y
Tsunoda, T
Yoshino, E
Bentley, DR
Deloukas, P
Hunt, S
Powell, D
Altshuler, D
Gabriel, SB
Qiu, RZ
[J]. NATURE, 2003, 426 (6968) : 789 - 796
[10] The association between mother and child MTHFR C677T polymorphisms, dietary folate intake and childhood atopy in a population-based, longitudinal birth cohort
Granell, R.
Heron, J.
Lewis, S.
Smith, G. D.
Sterne, J. A. C.
Henderson, J.
[J]. CLINICAL AND EXPERIMENTAL ALLERGY, 2008, 38 (02) : 320 - 328

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