@article {114,
	title = {Genetics of 35 blood and urine biomarkers in the UK Biobank.},
	journal = {Nat Genet},
	volume = {53},
	year = {2021},
	month = {2021 02},
	pages = {185-194},
	abstract = {<p>Clinical laboratory tests are a critical component of the continuum of care. We evaluate the genetic basis of 35 blood and urine laboratory measurements in the UK Biobank (n = 363,228 individuals). We identify 1,857 loci associated with at least one trait, containing 3,374 fine-mapped associations and additional sets of large-effect (>0.1 s.d.) protein-altering, human leukocyte antigen (HLA) and copy number variant (CNV) associations. Through Mendelian randomization (MR) analysis, we discover 51 causal relationships, including previously known agonistic effects of urate on gout and cystatin C on stroke. Finally, we develop polygenic risk scores (PRSs) for each biomarker and build {\textquoteright}multi-PRS{\textquoteright} models for diseases using 35 PRSs simultaneously, which improved chronic kidney disease, type 2 diabetes, gout and alcoholic cirrhosis genetic risk stratification in an independent dataset (FinnGen; n = 135,500) relative to single-disease PRSs. Together, our results delineate the genetic basis of biomarkers and their causal influences on diseases and improve genetic risk stratification for common diseases.</p>},
	keywords = {Biological Specimen Banks, Biomarkers, Cardiovascular Diseases, Diabetes Mellitus, Type 2, DNA Copy Number Variations, Genetic Pleiotropy, HLA Antigens, Humans, Linkage Disequilibrium, Liver-Specific Organic Anion Transporter 1, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Proteins, Renal Insufficiency, Chronic, Serine Endopeptidases, United Kingdom},
	issn = {1546-1718},
	doi = {10.1038/s41588-020-00757-z},
	author = {Sinnott-Armstrong, Nasa and Tanigawa, Yosuke and Amar, David and Mars, Nina and Benner, Christian and Aguirre, Matthew and Venkataraman, Guhan Ram and Wainberg, Michael and Ollila, Hanna M and Kiiskinen, Tuomo and Havulinna, Aki S and Pirruccello, James P and Qian, Junyang and Shcherbina, Anna and Rodriguez, Fatima and Assimes, Themistocles L and Agarwala, Vineeta and Tibshirani, Robert and Hastie, Trevor and Ripatti, Samuli and Pritchard, Jonathan K and Daly, Mark J and Rivas, Manuel A}
}
@article {96,
	title = {Sex-specific genetic effects across biomarkers.},
	journal = {Eur J Hum Genet},
	volume = {29},
	year = {2021},
	month = {2021 Jan},
	pages = {154-163},
	abstract = {<p>Sex differences have been shown in laboratory biomarkers; however, the extent to which this is due to genetics is unknown. In this study, we infer sex-specific genetic parameters (heritability and genetic correlation) across 33 quantitative biomarker traits in 181,064 females and 156,135 males from the UK Biobank study. We apply a Bayesian Mixture Model, Sex Effects Mixture Model~(SEMM), to Genome-wide Association Study summary statistics in order to (1) estimate the contributions of sex to the genetic variance of these biomarkers and (2) identify variants whose statistical association with these traits is sex-specific. We find that the genetics of most biomarker traits are shared between males and females, with the notable exception of testosterone, where we identify 119 female and 445 male-specific variants. These include protein-altering variants in steroid hormone production genes (POR, UGT2B7). Using the sex-specific variants as genetic instruments for Mendelian randomization, we find evidence for causal links between testosterone levels and height, body mass index, waist and hip circumference, and type 2 diabetes. We also show that sex-specific polygenic risk score models for testosterone outperform a combined model. Overall, these results demonstrate that while sex has a limited role in the genetics of most biomarker traits, sex plays an important role in testosterone genetics.</p>},
	issn = {1476-5438},
	doi = {10.1038/s41431-020-00712-w},
	author = {Flynn, Emily and Tanigawa, Yosuke and Rodriguez, Fatima and Altman, Russ B and Sinnott-Armstrong, Nasa and Rivas, Manuel A}
}
