The transferability of lipid loci across African, Asian and European cohorts

被引：16

作者：

Kuchenbaecker, Karoline ^{[1
,2
,3
]}

Telkar, Nikita ^{[4
]}

Reiker, Theresa ^{[3
,5
,6
,7
]}

Walters, Robin G. ^{[8
,9
,10
]}

Lin, Kuang ^{[9
,10
]}

Eriksson, Anders ^{[11
]}

Gurdasani, Deepti ^{[3
]}

Gilly, Arthur ^{[3
,12
]}

Southam, Lorraine ^{[3
,12
,13
]}

Tsafantakis, Emmanouil ^{[14
]}

Karaleftheri, Maria ^{[15
]}

Seeley, Janet ^{[16
,17
,18
,19
,20
]}

Kamali, Anatoli ^{[18
,19
,20
]}

Asiki, Gershim ^{[18
,19
,20
,21
,22
]}

Millwood, Iona Y. ^{[8
,9
,10
]}

Holmes, Michael ^{[8
,9
,10
]}

Du, Huaidong ^{[8
,9
,10
]}

Guo, Yu ^{[23
]}

Kumari, Meena ^{[24
]}

Dedoussis, George ^{[25
]}

Li, Liming ^{[26
]}

Chen, Zhengming ^{[9
,10
]}

Sandhu, Manjinder S. ^{[27
]}

Zeggini, Eleftheria ^{[3
,12
]}

Benzeval, Michaela ^{[24
]}

Burton, Jonathan ^{[24
]}

Buck, Nicholas ^{[24
]}

Jackle, Annette ^{[24
]}

Laurie, Heather ^{[24
]}

Lynn, Peter ^{[24
]}

Pudney, Stephen ^{[24
]}

Rabe, Birgitta ^{[24
]}

Wolke, Dieter ^{[28
]}

机构：

[1] UCL, Div Psychiat, London W1T 7NF, England

[2] UCL, Genet Inst, London WC1E 6BT, England

[3] Wellcome Sanger Inst, Dept Human Genet, Hinxton CB10 1SA, England

[4] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England

[5] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England

[6] Swiss Trop & Publ Hlth Inst, Basel, Switzerland

[7] Univ Basel, Basel, Switzerland

[8] Univ Oxford, MRC PHRU, Nuffield Dept Populat Hlth, Oxford, England

[9] Univ Oxford, Nuffield Dept Populat Hlth, CTSU, Oxford, England

[10] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England

[11] Kings Coll London, Dept Med & Mol Genet, London SE1 9RT, England

[12] German Res Ctr Environm Hlth, Inst Translat Genom, Helmholtz Zentrum Munchen, Neuherberg, Germany

[13] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[14] Anogia Med Ctr, Anogia 74051, Greece

[15] Echinos Med Ctr, Xanthi 67300, Greece

[16] London Sch Hyg & Trop Med, Dept Global Hlth & Dev, London WC1E 7HT, England

[17] London Sch Hyg & Trop Med, Fac Publ Hlth & Policy, London WC1E 7HT, England

[18] Uganda Virus Res Inst, MRC, Entebbe, Uganda

[19] London Sch Hyg MRC UVRI, Entebbe, Uganda

[20] LSHTM, Uganda Res Unit, Entebbe, Uganda

[21] African Populat & Hlth Res Ctr, Nairobi, Kenya

[22] Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden

[23] Chinese Acad Med Sci, Beijing 100730, Peoples R China

[24] Univ Essex, Inst Social & Econ Res, Wivenhoe Pk, Colchester CO4 35Q, Essex, England

[25] Harokopio Univ Athens, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece

[26] Peking Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Beijing 100191, Peoples R China

[27] Univ Cambridge, Dept Med, Cambridge CB2 0QQ, England

[28] Univ Warwick, Dept Psychol, Coventry CV4 7AL, W Midlands, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

英国惠康基金; 英国医学研究理事会; 欧洲研究理事会; 英国经济与社会研究理事会; 中国国家自然科学基金;

关键词：

GENETIC ASSOCIATIONS; WIDE ASSOCIATION; BLOOD-LIPIDS; MIXED-MODEL; VARIANTS; GENOMICS; BIOBANK; DISEASE; TRAITS; HEALTH;

D O I：

10.1038/s41467-019-12026-7

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：

Most genome-wide association studies are based on samples of European descent. We assess whether the genetic determinants of blood lipids, a major cardiovascular risk factor, are shared across populations. Genetic correlations for lipids between European-ancestry and Asian cohorts are not significantly different from 1. A genetic risk score based on LDL-cholesterol-associated loci has consistent effects on serum levels in samples from the UK, Uganda and Greece (r= 0.23-0.28, p < 1.9 x 10(-14)). Overall, there is evidence of reproducibility for -75% of the major lipid loci from European discovery studies, except triglyceride loci in the Ugandan samples (10% of loci). Individual transferable loci are identified using trans-ethnic colocalization. Ten of fourteen loci not transferable to the Ugandan population have pleiotropic associations with BMI in Europeans; none of the transferable loci do. The non-transferable loci might affect lipids by modifying food intake in environments rich in certain nutrients, which suggests a potential role for gene-environment interactions.

引用

页数：10

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