PMC:3480678 / 1777-5826 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3480678","sourcedb":"PMC","sourceid":"3480678","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3480678","text":"Introduction\nIn genetic epidemiological research, both case-control and case-parent trio designs have been used widely to evaluate genetic susceptibilities to human complex diseases and markers, such as single-nucleotide polymorphisms (SNPs), to localize disease gene variants [1-5]. The sample size for detecting associations between disease and SNP markers is known to be highly affected by disease prevalence, disease allele frequency, linkage disequilibrium (LD), inheritance models (e.g., additive, dominant, and multiplicative models), and effect size of the genetic variants (e.g., odds ratio, relative risk, etc.) [4, 6, 7]. Previous studies have shown that a population based case-control design can be more powerful than a family-based study design in identifying genes predisposing human complex traits, both for qualitative traits and for quantitative traits [8-11]. However, some studies reported that the case-parent design is much more powerful than the case-control design in evaluating genetic risk for common complex diseases, because case-control studies are susceptible to bias due to phenotype misclassification or population stratification [12, 13].\nRecently, genome-wide association studies (GWASs) using thousands of cases and controls reported many susceptibility SNPs for 237 human traits by the end of June, 2011 (www.genome.gov/GWAStudies). Since a GWAS evaluates hundreds of thousands of SNP markers, it requires a much larger sample size to achieve an adequate statistical power [14-18]. In genetic association studies, the observed signal for association is referred to be statistically significant if the p-value is less than a preset threshold value (α) of 0.05 to reject a null hypothesis of genetic association. Testing a large number of SNP markers leads to a large number of multiple comparisons and thus increases false positive rates. Either the Bonferroni correction or the false discovery rate is generally applied to avoid false positive (type I error) rates. However, the Bonferroni-corrected p-value, the significance threshold set to 0.05 divided by the total number of SNPs analyzed in a GWAS, is too strict to consider the correlations among SNP markers (e.g., p = 1 × 10-7 for 500,000 (500 K) SNPs, p = 5 × 10-8 for 1 million (M) SNPs) [16, 19]. Therefore, estimating a sufficient sample size to achieve adequate statistical power is critical in the design stage of genetic association [20-24].\nStatistical power is the probability to reject a null hypothesis (H0) while the alternative hypothesis (HA) is true. It is affected by many factors. For instance, a larger sample size is required to achieve sufficient statistical power. Although a researcher collects a large number of samples, all samples may not be necessary to be analyzed to detect evidence for association. A large sample size improves the ability of disease prediction; however, it is not cost-effective that a researcher genotypes more than the effective sample size [25]. Unless researchers estimate sample size and statistical power at the research design stage, it leads to wasted time and resources to collect samples. An effective sample size can be defined as the minimum number of samples that achieves adequate statistical power (e.g., 80% power). On the other hand, too small a sample size to detect true evidence for an association increases false negative rates and reduces the reliability of a study. False negative rates are increased by multiple factors that cause systematic biases, and such biases reduce statistical power [26]. The statistical power of 80% is used widely to avoid false negative associations and to determine a cost-effective sample size in large-scale association studies [7, 22, 23]. However, many researchers tend to overlook the importance of statistical power and sample size calculations.\nIn this study, we evaluated statistical power with increasing numbers of markers analyzed under various assumptions and compared the sample sizes required in case-control studies and case-parent studies.","divisions":[{"label":"Title","span":{"begin":0,"end":12}}],"tracks":[{"project":"2_test","denotations":[{"id":"23105939-11253062-44845521","span":{"begin":278,"end":279},"obj":"11253062"},{"id":"23105939-12446984-44845521","span":{"begin":278,"end":279},"obj":"12446984"},{"id":"23105939-11882781-44845521","span":{"begin":278,"end":279},"obj":"11882781"},{"id":"23105939-14614239-44845521","span":{"begin":278,"end":279},"obj":"14614239"},{"id":"23105939-18591452-44845521","span":{"begin":278,"end":279},"obj":"18591452"},{"id":"23105939-14614239-44845522","span":{"begin":623,"end":624},"obj":"14614239"},{"id":"23105939-12603052-44845523","span":{"begin":626,"end":627},"obj":"12603052"},{"id":"23105939-12916022-44845524","span":{"begin":629,"end":630},"obj":"12916022"},{"id":"23105939-9872982-44845525","span":{"begin":872,"end":873},"obj":"9872982"},{"id":"23105939-10866211-44845525","span":{"begin":872,"end":873},"obj":"10866211"},{"id":"23105939-16258007-44845525","span":{"begin":872,"end":873},"obj":"16258007"},{"id":"23105939-19172087-44845526","span":{"begin":1163,"end":1165},"obj":"19172087"},{"id":"23105939-20383776-44845527","span":{"begin":1167,"end":1169},"obj":"20383776"},{"id":"23105939-17725844-44845528","span":{"begin":1510,"end":1512},"obj":"17725844"},{"id":"23105939-17947991-44845528","span":{"begin":1510,"end":1512},"obj":"17947991"},{"id":"23105939-19492015-44845528","span":{"begin":1510,"end":1512},"obj":"19492015"},{"id":"23105939-19649321-44845528","span":{"begin":1510,"end":1512},"obj":"19649321"},{"id":"23105939-20562874-44845528","span":{"begin":1510,"end":1512},"obj":"20562874"},{"id":"23105939-19492015-44845529","span":{"begin":2285,"end":2287},"obj":"19492015"},{"id":"23105939-17426422-44845530","span":{"begin":2289,"end":2291},"obj":"17426422"},{"id":"23105939-12225610-44845531","span":{"begin":2435,"end":2437},"obj":"12225610"},{"id":"23105939-12603051-44845531","span":{"begin":2435,"end":2437},"obj":"12603051"},{"id":"23105939-15339280-44845531","span":{"begin":2435,"end":2437},"obj":"15339280"},{"id":"23105939-18477402-44845531","span":{"begin":2435,"end":2437},"obj":"18477402"},{"id":"23105939-20718045-44845532","span":{"begin":2985,"end":2987},"obj":"20718045"},{"id":"23105939-15953257-44845533","span":{"begin":3557,"end":3559},"obj":"15953257"},{"id":"23105939-12916022-44845534","span":{"begin":3725,"end":3726},"obj":"12916022"},{"id":"23105939-15339280-44845535","span":{"begin":3728,"end":3730},"obj":"15339280"}],"attributes":[{"subj":"23105939-11253062-44845521","pred":"source","obj":"2_test"},{"subj":"23105939-12446984-44845521","pred":"source","obj":"2_test"},{"subj":"23105939-11882781-44845521","pred":"source","obj":"2_test"},{"subj":"23105939-14614239-44845521","pred":"source","obj":"2_test"},{"subj":"23105939-18591452-44845521","pred":"source","obj":"2_test"},{"subj":"23105939-14614239-44845522","pred":"source","obj":"2_test"},{"subj":"23105939-12603052-44845523","pred":"source","obj":"2_test"},{"subj":"23105939-12916022-44845524","pred":"source","obj":"2_test"},{"subj":"23105939-9872982-44845525","pred":"source","obj":"2_test"},{"subj":"23105939-10866211-44845525","pred":"source","obj":"2_test"},{"subj":"23105939-16258007-44845525","pred":"source","obj":"2_test"},{"subj":"23105939-19172087-44845526","pred":"source","obj":"2_test"},{"subj":"23105939-20383776-44845527","pred":"source","obj":"2_test"},{"subj":"23105939-17725844-44845528","pred":"source","obj":"2_test"},{"subj":"23105939-17947991-44845528","pred":"source","obj":"2_test"},{"subj":"23105939-19492015-44845528","pred":"source","obj":"2_test"},{"subj":"23105939-19649321-44845528","pred":"source","obj":"2_test"},{"subj":"23105939-20562874-44845528","pred":"source","obj":"2_test"},{"subj":"23105939-19492015-44845529","pred":"source","obj":"2_test"},{"subj":"23105939-17426422-44845530","pred":"source","obj":"2_test"},{"subj":"23105939-12225610-44845531","pred":"source","obj":"2_test"},{"subj":"23105939-12603051-44845531","pred":"source","obj":"2_test"},{"subj":"23105939-15339280-44845531","pred":"source","obj":"2_test"},{"subj":"23105939-18477402-44845531","pred":"source","obj":"2_test"},{"subj":"23105939-20718045-44845532","pred":"source","obj":"2_test"},{"subj":"23105939-15953257-44845533","pred":"source","obj":"2_test"},{"subj":"23105939-12916022-44845534","pred":"source","obj":"2_test"},{"subj":"23105939-15339280-44845535","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93b3ec","default":true}]}]}}