Showing papers by "Thorgeir E. Thorgeirsson published in 2011"
University of London1, Imperial College London2, Imperial College Healthcare3, Mahidol University4, University of California, San Francisco5, Virginia Commonwealth University6, Erasmus University Rotterdam7, Uppsala University8, University of Groningen9, University of Paris-Sud10, French Institute of Health and Medical Research11, Utrecht University12, Centre national de la recherche scientifique13, University of Mainz14, Indiana University15, University of Tartu16, University of Salamanca17, University of California, Los Angeles18, Pierre-and-Marie-Curie University19, University of Iceland20, University of Oulu21, University of Washington22, University of Connecticut23, VU University Amsterdam24, University of Helsinki25, University of Cambridge26, King's College London27, University of Turin28, University of Oxford29, University of Erlangen-Nuremberg30, QIMR Berghofer Medical Research Institute31, Semmelweis University32, Leiden University33, Wellcome Trust Sanger Institute34, GlaxoSmithKline35, Leipzig University36, University of Lausanne37, Ludwig Maximilian University of Munich38
TL;DR: A genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption among 12 population-based samples of European ancestry finds a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples and finds a regulator of alcohol consumption.
Abstract: Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of similar to 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Downregulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.
265 citations
01 Jan 2011
225 citations
deCODE genetics1, Aarhus University Hospital2, Aarhus University3, University of Oslo4, Copenhagen University Hospital5, University of Iceland6, Utrecht University7, University of California, Los Angeles8, University of Bonn9, Wellcome Trust Sanger Institute10, University of Helsinki11, National Institutes of Health12, Ludwig Maximilian University of Munich13, Glostrup Hospital14, Heidelberg University15, Semmelweis University16, University of Verona17, Radboud University Nijmegen Medical Centre18, Russian Academy19, King's College London20, Sichuan University21, Royal Cornhill Hospital22, Karolinska Institutet23
TL;DR: As it has been proposed that variants such as rs1344706[T]—common and with low relative risk—may also serve to identify regions harboring less common, higher-risk susceptibility alleles, ZNF804A is searched for large copy number variants (CNVs) in psychosis patients and patients with other psychiatric disorders and 39 481 controls.
Abstract: A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10(-8)) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10(-7), and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10(-8). In this study, using 5164 schizophrenia cases and 20,709 controls, we replicated the association with schizophrenia (odds ratio OR = 1.08, P = 0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N = 609, OR = 1.09, P = 0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]-common and with low relative risk-may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39,481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P = 0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P = 0.0016 for association with the larger set of psychiatric disorders).
164 citations
TL;DR: A meta-analysis of four genome-wide association studies of coffee consumption among coffee drinkers from Iceland, The Netherlands, the Sorbs Slavonic population isolate in Germany and the USA found two sequence variants significantly associated with increased coffee consumption.
Abstract: Coffee is the most commonly used stimulant and caffeine is its main psychoactive ingredient. The heritability of coffee consumption has been estimated at around 50%. We performed a meta-analysis of four genome-wide association studies of coffee consumption among coffee drinkers from Iceland (n = 2680), The Netherlands (n = 2791), the Sorbs Slavonic population isolate in Germany (n = 771) and the USA (n = 369) using both directly genotyped and imputed single nucleotide polymorphisms (SNPs) (2.5 million SNPs). SNPs at the two most significant loci were also genotyped in a sample set from Iceland (n = 2430) and a Danish sample set consisting of pregnant women (n = 1620). Combining all data, two sequence variants significantly associated with increased coffee consumption: rs2472297-T located between CYP1A1 and CYP1A2 at 15q24 (P = 5.4 · 10(-14)) and rs6968865-T near aryl hydrocarbon receptor (AHR) at 7p21 (P = 2.3 · 10(-11)). An effect of ∼0.2 cups a day per allele was observed for both SNPs. CYP1A2 is the main caffeine metabolizing enzyme and is also involved in drug metabolism. AHR detects xenobiotics, such as polycyclic aryl hydrocarbons found in roasted coffee, and induces transcription of CYP1A1 and CYP1A2. The association of these SNPs with coffee consumption was present in both smokers and non-smokers.
117 citations
TL;DR: The data show that 1 or more lung cancer risk variants of genome-wide significance and distinct from the coding variants in TP53BP1 are located at 15q15.2.
Abstract: Genome-wide association studies (GWAS) have identified 3 genomic regions, at 15q24-25.1, 5p15.33, and 6p21.33, which associate with the risk of lung cancer. Large meta-analyses of GWA data have failed to find additional associations of genome-wide significance. In this study, we sought to confirm 7 variants with suggestive association to lung cancer (P < 10(-5)) in a recently published meta-analysis. In a GWA dataset of 1,447 lung cancer cases and 36,256 controls in Iceland, 3 correlated variants on 15q15.2 (rs504417, rs11853991, and rs748404) showed a significant association with lung cancer, whereas rs4254535 on 2p14, rs1530057 on 3p24.1, rs6438347 on 3q13.31, and rs1926203 on 10q23.31 did not. The most significant variant, rs748404, was genotyped in an additional 1,299 lung cancer cases and 4,102 controls from the Netherlands, Spain, and the United States and the results combined with published GWAS data. In this analysis, the T allele of rs748404 reached genome-wide significance (OR = 1.15, P = 1.1 × 10(-9)). Another variant at the same locus, rs12050604, showed association with lung cancer (OR = 1.09, 3.6 × 10(-6)) and remained significant after adjustment for rs748404 and vice versa. rs748404 is located 140 kb centromeric of the TP53BP1 gene that has been implicated in lung cancer risk. Two fully correlated, nonsynonymous coding variants in TP53BP1, rs2602141 (Q1136K) and rs560191 (E353D) showed association with lung cancer in our sample set; however, this association did not remain significant after adjustment for rs748404. Our data show that 1 or more lung cancer risk variants of genome-wide significance and distinct from the coding variants in TP53BP1 are located at 15q15.2.
25 citations
11 citations
Patent•
24 Feb 2011
TL;DR: In this paper, the authors disclosed certain genetic variants that are susceptibility variants for lung cancer and proposed a risk assessment and diagnostic methods using the variants using the genetic variants and further related to kits for use in risk assessment of lung cancer.
Abstract: The present invention discloses certain genetic variants that are susceptibility variants for lung cancer. The invention relates to risk assessment and diagnostic methods using the variants. The invention further relates to kits for use in risk assessment of lung cancer.
3 citations
Patent•
19 Jan 2011
TL;DR: In this article, the authors disclosed certain genetic variants as susceptibility variants for peripheral arterial disease (PAD) and abdominal aortic aneurysm (AAA) and related to risk management using such variants.
Abstract: The present invention discloses certain genetic variants as susceptibility variants for peripheral arterial disease (PAD) and abdominal aortic aneurysm (AAA). The invention relates to risk management using such variants. The invention further relates to kits for use in risk assessment of PAD and AAA.