Dataset Information

Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.

ABSTRACT: Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1?s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

SUBMITTER: Soler Artigas M

PROVIDER: S-EPMC4686825 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.

Soler Artigas María M Wain Louise V LV Miller Suzanne S Kheirallah Abdul Kader AK Huffman Jennifer E JE Ntalla Ioanna I Shrine Nick N Obeidat Ma'en M Trochet Holly H McArdle Wendy L WL Alves Alexessander Couto AC Hui Jennie J Zhao Jing Hua JH Joshi Peter K PK Teumer Alexander A Albrecht Eva E Imboden Medea M Rawal Rajesh R Lopez Lorna M LM Marten Jonathan J Enroth Stefan S Surakka Ida I Polasek Ozren O Lyytikäinen Leo-Pekka LP Granell Raquel R Hysi Pirro G PG Flexeder Claudia C Mahajan Anubha A Beilby John J Bossé Yohan Y Brandsma Corry-Anke CA Campbell Harry H Gieger Christian C Gläser Sven S González Juan R JR Grallert Harald H Hammond Chris J CJ Harris Sarah E SE Hartikainen Anna-Liisa AL Heliövaara Markku M Henderson John J Hocking Lynne L Horikoshi Momoko M Hutri-Kähönen Nina N Ingelsson Erik E Johansson Åsa Å Kemp John P JP Kolcic Ivana I Kumar Ashish A Lind Lars L Melén Erik E Musk Arthur W AW Navarro Pau P Nickle David C DC Padmanabhan Sandosh S Raitakari Olli T OT Ried Janina S JS Ripatti Samuli S Schulz Holger H Scott Robert A RA Sin Don D DD Starr John M JM Viñuela Ana A Völzke Henry H Wild Sarah H SH Wright Alan F AF Zemunik Tatijana T Jarvis Deborah L DL Spector Tim D TD Evans David M DM Lehtimäki Terho T Vitart Veronique V Kähönen Mika M Gyllensten Ulf U Rudan Igor I Deary Ian J IJ Karrasch Stefan S Probst-Hensch Nicole M NM Heinrich Joachim J Stubbe Beate B Wilson James F JF Wareham Nicholas J NJ James Alan L AL Morris Andrew P AP Jarvelin Marjo-Riitta MR Hayward Caroline C Sayers Ian I Strachan David P DP Hall Ian P IP Tobin Martin D MD

Nature communications 20151204

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN ...[more]

PMID: 26635082

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Project description:Genome-wide association (GWA) studies have been limited by the reliance on common variants present on microarrays or imputable from the HapMap Project data. More recently, the completion of the 1000 Genomes Project has provided variant and haplotype information for several million variants derived from sequencing over 1,000 individuals. To help understand the extent to which more variants (including low frequency (1% ? MAF <5%) and rare variants (<1%)) can enhance previously identified associations and identify novel loci, we selected 93 quantitative circulating factors where data was available from the InCHIANTI population study. These phenotypes included cytokines, binding proteins, hormones, vitamins and ions. We selected these phenotypes because many have known strong genetic associations and are potentially important to help understand disease processes. We performed a genome-wide scan for these 93 phenotypes in InCHIANTI. We identified 21 signals and 33 signals that reached P<5×10(-8) based on HapMap and 1000 Genomes imputation, respectively, and 9 and 11 that reached a stricter, likely conservative, threshold of P<5×10(-11) respectively. Imputation of 1000 Genomes genotype data modestly improved the strength of known associations. Of 20 associations detected at P<5×10(-8) in both analyses (17 of which represent well replicated signals in the NHGRI catalogue), six were captured by the same index SNP, five were nominally more strongly associated in 1000 Genomes imputed data and one was nominally more strongly associated in HapMap imputed data. We also detected an association between a low frequency variant and phenotype that was previously missed by HapMap based imputation approaches. An association between rs112635299 and alpha-1 globulin near the SERPINA gene represented the known association between rs28929474 (MAF?=?0.007) and alpha1-antitrypsin that predisposes to emphysema (P?=?2.5×10(-12)). Our data provide important proof of principle that 1000 Genomes imputation will detect novel, low frequency-large effect associations.

Dataset Information

Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.

Publications

Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.

Similar Datasets

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