Evidence for sex-specific genetic architectures across a spectrum of human complex traits

Phenotype quality control

We obtained measures for waist circumference (UKBID 48), hip circumference (UKBID 49), standing height (UKBID 50), BMI (UKBID 21001), body fat percentage (UKBID 23099), basal metabolic rate (UKBID 23105), self-reported age of completion of full-time education for individuals without university education (UKBID 845), number of offspring (UKBID 2405 and 2734), fluid intelligence score (UKBID 20016), diastolic blood pressure (UKBID 4079), systolic blood pressure (UKBID 4080), forced volume vital capacity (UKBID 3062), forced expiratory volume in 1 s (UKBID 3063), peak expiratory flow (UKBID 3064), and self-reported overall health (UKBID 2178). Further information about these, including details of measurement protocols, can be accessed through the UK Biobank resource (http://biobank.ctsu.ox.ac.uk/crystal/index.cgi) using the provided UKBID. We additionally computed several derived phenotypes based on information contained in the UK Biobank. Specifically, we computed WHR and FEV₁/FVC as ratios of WC, HC, FEV₁ and FVC, respectively, and furthermore rescaled BMR to have a standard deviation of 1 in the population due to numerical problems in model fitting on the measurement scale. LRS was calculated as the self-reported number of offspring for individuals who have completed their reproductive life. These were defined as men aged over 60 years and women who reported either having had their menopause or undergone a hysterectomy or who were aged over 60 years. We furthermore excluded individuals who reported having had in excess of 15 offspring. We constructed a cognitive function score (CF score) as the first principal component of several cognitive measures, specifically the results of a reaction time test (UKBID 20023), time to complete, and number of incorrect guesses during completion of a pairs matching test (UKBID 400 and 399). Prior to PCA we excluded individuals who were more than 5 standard deviations from the population for any of these measures. The number of pack years of smoking was calculated based on smoking history information as described elsewhere (http://biobank.ctsu.ox.ac.uk/crystal/field.cgi?id=20161). Self-reported overall health status was measured as the answer to the question “In general how would you rate your overall health?” excluding “Do not know”/“Prefer not to answer” we coded the possible four answers as numerical values 1 (“Excellent”) to 4 (“Poor”) and fitted all models on this observed scale. For the cardiovascular phenotypes (BP_dia and BP_sys) we excluded all individuals who reported taking blood pressure medication (UKBID 6153 and 6177). We removed outliers from WC, HC, height, BMI, BF%, BMR, WHR, education age, BP_dia, BP_sys, FVC, FEV₁, PEF, and FEV₁/FVC, defining outliers as males and females who were outside ±3 standard deviations from their gender mean of all the individuals in the white British cohort.