In search of the genetic variants of human sex ratio at birth: Was Fisher wrong about sex ratio evolution?

The human sex ratio (fraction of males) at birth is close to 0.5 at the population level, an observation commonly explained by Fisher's principle. However, past human studies yielded conflicting results regarding the existence of sex ratio-influencing mutations-a prerequisite to Fisher’s principle, raising the question of whether the nearly even population sex ratio is instead dictated by the random X/Y chromosome segregation in male meiosis. Here we show that, because a person’s offspring sex ratio (OSR) has an enormous measurement error, a gigantic sample is required to detect OSR-influencing genetic variants. Conducting a UK Biobank-based genome-wide association study that is more powerful than previous studies, we detect an OSR-associated genetic variant, which awaits verification in independent samples. Given the abysmal precision in measuring OSR, it is unsurprising that the estimated heritability of OSR is effectively zero. We further show that OSR’s estimated heritability would ..., GWAS:
When conducting the GWAS in the UKB, we did not simply use the sibling sex ratio as the trait, because of the difficulty in accounting for different estimation errors of the sibling sex ratio for different families as a result of the variation in family size.  For example, individual A has one brother and zero sister, while individual B has four brothers and one sister.  Although A has a higher sibling sex ratio than B, B’s siblings obviously provide stronger evidence for a male-biased sibling sex ratio than A’s siblings.  To properly weigh the data by the family size, we considered the birth of each sibling as an independent event.  In the above example, we would associate A’s genotype with one male birth and associate B’s genotype with four male births and one female birth.  In GWAS, a male birth is coded as 1 and a female birth is coded as 0.  The UKB participants have a total of 873,715 full siblings, leading to an unprecedented statistical power.  In our GWAS in the UKB, we i..., , # In search of the genetic variants of human sex ratio at birth: Was Fisher wrong about sex ratio evolution?

[https://doi.org/10.5061/dryad.vdncjsz43](https://doi.org/10.5061/dryad.vdncjsz43)

## Description of the data and file structure

GWAS summary statistics and simulation data of the paper \"In search of the genetic variants of human sex ratio at birth: Was Fisher wrong about sex ratio evolution?\"

### Files and variables

#### File: Human\_sex\_ratio\_scrit.zip

**Description:** Scripts for the project. For descriptions of each script files, see README.md in the zip file or [https://github.com/song88180/Human_sex_ratio](https://github.com/song88180/Human_sex_ratio)

#### File: GWAS\_OSR\_cov\_logistic.tsv

**Description:** GWAS summary statistics of offspring sex ratio. Cells with \"NA\" means the value is not available. 

##### Variables

* CHROM: chromosome number
* POS: SNP position (GRCh37)
* ID: rsid of the SNP
* REF: reference allele
* ALT: alternative allele
* P: P-value
* t...