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11.	Sofer, Tamar, et al. (author) A fully adjusted two-stage procedure for rank-normalization in genetic association studies 2019 In: Genetic Epidemiology. - : John Wiley & Sons. - 0741-0395 .- 1098-2272. ; 43:3, s. 263-275 Journal article (peer-reviewed)abstract When testing genotype–phenotype associations using linear regression, departure of the trait distribution from normality can impact both Type I error rate control and statistical power, with worse consequences for rarer variants. Because genotypes are expected to have small effects (if any) investigators now routinely use a two‐stage method, in which they first regress the trait on covariates, obtain residuals, rank‐normalize them, and then use the rank‐normalized residuals in association analysis with the genotypes. Potential confounding signals are assumed to be removed at the first stage, so in practice, no further adjustment is done in the second stage. Here, we show that this widely used approach can lead to tests with undesirable statistical properties, due to both combination of a mis‐specified mean–variance relationship and remaining covariate associations between the rank‐normalized residuals and genotypes. We demonstrate these properties theoretically, and also in applications to genome‐wide and whole‐genome sequencing association studies. We further propose and evaluate an alternative fully adjusted two‐stage approach that adjusts for covariates both when residuals are obtained and in the subsequent association test. This method can reduce excess Type I errors and improve statistical power.
12.	Amos, Christopher I, et al. (author) Genome-wide association study identifies novel loci predisposing to cutaneous melanoma 2011 In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:24, s. 23-5012 Journal article (peer-reviewed)abstract We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.
13.	Meschia, James F, et al. (author) Stroke Genetics Network (SiGN) study: design and rationale for a genome-wide association study of ischemic stroke subtypes. 2013 In: Stroke; a journal of cerebral circulation. - 1524-4628. ; 44:10, s. 2694-702 Journal article (peer-reviewed)abstract Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke.

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Result 11-13 of 13

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Type of publication: journal article (13)

Type of content: peer-reviewed (13)

Author/Editor: Laurie, Cathy C (11); Rotter, Jerome I. (5); Kooperberg, Charles (5); Fornage, Myriam (5); Franceschini, Nora (5); Peters, Annette (4); show more...; Strauch, Konstantin (4); Waldenberger, Melani ... (4); Harris, Tamara B (4); Launer, Lenore J (4); Loos, Ruth J F (4); Psaty, Bruce M (4); Gudnason, Vilmundur (4); Lind, Lars (3); Raitakari, Olli T (3); Wareham, Nicholas J. (3); Shu, Xiao-Ou (3); van Duijn, Cornelia ... (3); Zhao, Wei (3); Nelson, Christopher ... (3); Gieger, Christian (3); Martin, Nicholas G. (3); Samani, Nilesh J. (3); Mahajan, Anubha (3); Caulfield, Mark J. (3); Munroe, Patricia B. (3); Meitinger, Thomas (3); Lehtimaki, Terho (3); Zhao, Jing Hua (3); Kritchevsky, Stephen ... (3); Liu, Yongmei (3); Rich, Stephen S (3); Uitterlinden, André ... (3); Morrison, Alanna C (3); Hayward, Caroline (3); Elliott, Paul (3); Aschard, Hugues (3); Arking, Dan E. (3); Chen, Yii-Der Ida (3); van der Most, Peter ... (3); Cupples, L. Adrienne (3); Boerwinkle, Eric (3); van der Harst, Pim (3); Liu, Jianjun (3); Ntalla, Ioanna (3); Giedraitis, Vilmanta ... (3); Smith, Albert V (3); Snieder, Harold (3); Lindgren, Cecilia M. (3); Morris, Andrew P. (3); show less...

University: Lund University (6); Umeå University (5); Uppsala University (4); Karolinska Institutet (4); University of Gothenburg (2); Stockholm University (2); show more...; Högskolan Dalarna (2); Linköping University (1); Swedish University of Agricultural Sciences (1); show less...

Language: English (13)

Research subject (UKÄ/SCB): Medical and Health Sciences (11); Natural sciences (2)

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