Filtering important SNPs

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Filtering important SNPs from population datasets using allele frequency (AF) and minor

allele frequency (MAF) involves several steps:

1. **Data Preparation:** Obtain a dataset containing genetic information from the population
of interest, typically in the form of variant call format (VCF) files or genotype data.

2. **Calculate Allele Frequency:** Calculate the allele frequency for each SNP in your
dataset. This can be done by counting the number of alleles of each type (e.g., reference allele
and alternate allele) and dividing by the total number of alleles sampled.

3. **Calculate Minor Allele Frequency:** Determine the minor allele for each SNP (the less
common allele) and calculate its frequency in the dataset. The minor allele frequency is the
frequency of the less common allele among the alleles observed.

4. **Set Thresholds:** Decide on thresholds for allele frequency and minor allele frequency
based on your research question and study design. These thresholds will depend on factors
such as the genetic architecture of the trait or disease you're studying, the size and diversity of
the population, and the desired balance between inclusivity and specificity.

5. **Filtering:** Apply the thresholds to filter out SNPs that do not meet your criteria. SNPs
with allele frequencies or minor allele frequencies below the specified thresholds may be
excluded from further analysis.

6. **Additional Filters:** Consider applying additional filters based on other criteria relevant
to your study, such as linkage disequilibrium (LD) pruning, Hardy-Weinberg equilibrium
(HWE), and quality control metrics.

7. **Prioritize SNPs:** Prioritize the remaining SNPs based on factors such as known
biological relevance, functional annotations, and association with traits or diseases of interest.

8. **Validation:** Validate the filtered SNPs using independent datasets or experimental


validation methods, if possible, to ensure the reliability of your results.

By following these steps, you can effectively filter out important SNPs from population
datasets based on allele frequency and minor allele frequency, while considering other
relevant factors for your study.

Criteria for threshold values:

Determining the frequency thresholds for allele frequency (AF) and minor allele frequency
(MAF) depends on several factors, including the goals of your study, the genetic architecture
of the trait or disease you're studying, the characteristics of the population, and the statistical
power of your analysis. Here are some considerations for determining frequency thresholds:
1. **Study Design and Goals:** Consider the objectives of your study. Are you interested in
common variants associated with common diseases, rare variants associated with rare
diseases, or something in between? The frequency thresholds may vary depending on whether
you're conducting a genome-wide association study (GWAS), a rare variant analysis, or
another type of study. Maybe common variants but looking at the differences between the
super populations that will cause disease

2. **Genetic Architecture:** The genetic architecture of the trait or disease can influence the
choice of frequency thresholds. For traits or diseases influenced by common variants with
small effects, you may prioritize SNPs with higher allele frequencies. Conversely, for traits or
diseases influenced by rare variants with larger effects, you may focus on SNPs with lower
allele frequencies. Determine if T2D and AD are caused by common variants or rare variants,
to determine what varainats are important to look for

3. **Population Characteristics:** Consider the characteristics of the population being


studied. Population-specific allele frequencies can vary due to factors such as genetic drift,
population bottlenecks, and admixture. If your study focuses on a specific population or
ancestry group, you may need to set frequency thresholds based on allele frequencies
observed in that population.

4. **Statistical Power:** Consider the statistical power of your analysis. SNPs with higher
allele frequencies generally have greater statistical power to detect associations with traits or
diseases. Setting frequency thresholds too low may result in an excess of false positives,
while setting them too high may lead to missed associations.

5. **Balance between Sensitivity and Specificity:** Find a balance between sensitivity (the
ability to detect true associations) and specificity (the ability to exclude false associations).
Adjust the frequency thresholds to optimize this balance based on your study objectives and
the expected effect sizes of the variants you're investigating.

6. **Previous Literature:** Review previous studies and literature relevant to your research
topic. Look for guidance on frequency thresholds used in similar studies and consider
adopting similar thresholds if appropriate.

7. **Validation:** Consider the need for validation or replication of your findings. If your
study identifies associations with SNPs above your initial frequency thresholds, you may
want to validate these associations in independent datasets or through experimental validation
methods.

By considering these factors, you can determine appropriate frequency thresholds for allele
frequency and minor allele frequency in your dataset, ensuring that they are tailored to the
specific requirements and objectives of your study.

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