From sexless to sexy: Why it is time for human genetics to consider and report analyses of sex.


:Science has come a long way with regard to the consideration of sex differences in clinical and preclinical research, but one field remains behind the curve: human statistical genetics. The goal of this commentary is to raise awareness and discussion about how to best consider and evaluate possible sex effects in the context of large-scale human genetic studies. Over the course of this commentary, we reinforce the importance of interpreting genetic results in the context of biological sex, establish evidence that sex differences are not being considered in human statistical genetics, and discuss how best to conduct and report such analyses. Our recommendation is to run stratified analyses by sex no matter the sample size or the result and report the findings. Summary statistics from stratified analyses are helpful for meta-analyses, and patterns of sex-dependent associations may be hidden in a combined dataset. In the age of declining sequencing costs, large consortia efforts, and a number of useful control samples, it is now time for the field of human genetics to appropriately include sex in the design, analysis, and reporting of results.


Biol Sex Differ


Powers MS,Smith PH,McKee SA,Ehringer MA




Has Abstract


2017-05-03 00:00:00










  • A developmental sex difference in hippocampal neurogenesis is mediated by endogenous oestradiol.

    abstract:BACKGROUND:Oestradiol is a steroid hormone that exerts extensive influence on brain development and is a powerful modulator of hippocampal structure and function. The hippocampus is a critical brain region regulating complex cognitive and emotional responses and is implicated in the aetiology of several mental health d...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Bowers JM,Waddell J,McCarthy MM

    更新日期:2010-11-22 00:00:00

  • Fetal growth outcomes following peri-implantation exposure of Long-Evans rats to noise and ozone differ by sex.

    abstract:BACKGROUND:Exposure to air pollution and high levels of noise have both been independently associated with the development of adverse pregnancy outcomes including low birth weight. However, exposure to such environmental stressors rarely occurs in isolation and is often co-localized, especially in large urban areas. M...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Miller CN,Kodavanti UP,Stewart EJ,Schladweiler MC,Richards JH,Snow SJ,Henriquez AR,Oshiro WM,Farraj AK,Hazari MS,Dye JA

    更新日期:2019-12-02 00:00:00

  • Sex differences in the association of phospholipids with components of the metabolic syndrome in young adults.

    abstract:BACKGROUND:There are differences in the prevalence and severity of diseases between males, females not taking hormonal contraceptives (non-HC females) and females taking hormonal contraceptives (HC females). The aim of this study was to identify sex-specific differences in the metabolome and its relation to components ...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Rauschert S,Uhl O,Koletzko B,Mori TA,Beilin LJ,Oddy WH,Hellmuth C

    更新日期:2017-03-28 00:00:00

  • Sex-specific effects of dietary fatty acids on saliva cortisol and social behavior in guinea pigs under different social environmental conditions.

    abstract:BACKGROUND:Unbalanced dietary intakes of saturated (SFAs) and polyunsaturated (PUFAs) fatty acids can profoundly influence the hypothalamic-pituitary-adrenal (HPA)-axis and glucocorticoid secretions in relation to behavioral performances. The beneficial effects of higher dietary PUFA intakes and PUFA:SFA ratios may als...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Nemeth M,Millesi E,Puehringer-Sturmayr V,Kaplan A,Wagner KH,Quint R,Wallner B

    更新日期:2016-09-22 00:00:00

  • Sex-specific association between the gut microbiome and high-fat diet-induced metabolic disorders in mice.

    abstract:BACKGROUND:Accumulating evidence indicates that high-fat diet (HFD)-induced metabolic disorders are associated with dysbiosis of the gut microbiota. However, the sex-specific characteristics of the gut microbiota and its association with a sexually dimorphic response to a HFD remain unclear. METHODS:Male and female mi...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Peng C,Xu X,Li Y,Li X,Yang X,Chen H,Zhu Y,Lu N,He C

    更新日期:2020-01-20 00:00:00

  • Is sex a proxy for mechanical variables during an upper limb repetitive movement task? An investigation of the effects of sex and of anthropometric load on muscle fatigue.

    abstract:BACKGROUND:Women report more work-related pain and neck/shoulder musculoskeletal disorders than men. For the same absolute workload, due to lower strength, females generally work at a higher relative intensity, which could induce more fatigue. However, the arm's anthropometric load (AL) of men is higher. Therefore, sim...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Slopecki M,Messing K,Côté JN

    更新日期:2020-10-30 00:00:00

  • Sex-specific regulation of chemokine Cxcl5/6 controls neutrophil recruitment and tissue injury in acute inflammatory states.

    abstract:BACKGROUND:Tissue infiltration by neutrophils during acute inflammatory states causes substantial tissue injury. While the magnitude of tissue neutrophil accumulation in innate immune responses is profoundly greater in males than females, fundamental aspects of the molecular mechanisms underlying these sex differences ...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Madalli S,Beyrau M,Whiteford J,Duchene J,Singh Nandhra I,Patel NS,Motwani MP,Gilroy DW,Thiemermann C,Nourshargh S,Scotland RS

    更新日期:2015-11-26 00:00:00

  • Severe pulmonary hypertension in aging female apolipoprotein E-deficient mice is rescued by estrogen replacement therapy.

    abstract:BACKGROUND:Apolipoprotein E (ApoE) is a multifunctional protein, and its deficiency leads to the development of atherosclerosis in mice. Patients with pulmonary hypertension (PH) have reduced expression of ApoE in lung tissue. ApoE is known to inhibit endothelial and smooth muscle cell proliferation and has anti-inflam...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Umar S,Partow-Navid R,Ruffenach G,Iorga A,Moazeni S,Eghbali M

    更新日期:2017-03-20 00:00:00

  • Genetic-gonadal-genitals sex (3G-sex) and the misconception of brain and gender, or, why 3G-males and 3G-females have intersex brain and intersex gender.

    abstract::The categorization of individuals as "male" or "female" is based on chromosome complement and gonadal and genital phenotype. This combined genetic-gonadal-genitals sex, here referred to as 3G-sex, is internally consistent in ~99% of humans (i.e., one has either the "female" form at all levels, or the "male" form at al...

    journal_title:Biology of sex differences

    pub_type: 社论


    authors: Joel D

    更新日期:2012-12-17 00:00:00

  • Lean mass mediates the relation between temporal summation of pain and sex in young healthy adults.

    abstract:BACKGROUND:Previous studies have shown that women experience greater temporal summation (TS) of pain than men using a repetitive thermal stimulus. These studies, however, did not individualize the thermal stimulus to each subject's thermal pain sensitivity. The aim of this study was to investigate sex differences in TS...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Awali A,Alsouhibani AM,Hoeger Bement M

    更新日期:2018-09-15 00:00:00

  • Sex differences in microRNA-mRNA networks: examination of novel epigenetic programming mechanisms in the sexually dimorphic neonatal hypothalamus.

    abstract:BACKGROUND:Sexual differentiation of the male brain, and specifically the stress circuitry in the hypothalamus, is primarily driven by estrogen exposure during the perinatal period. Surprisingly, this single hormone promotes diverse programs of sex-specific development that vary widely between different cell types and ...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Morgan CP,Bale TL

    更新日期:2017-08-15 00:00:00

  • Obesity: sex and sympathetics.

    abstract::Obesity increases sympathetic nerve activity (SNA) in men, but not women. Here, we review current evidence suggesting that sexually dimorphic sympathoexcitatory responses to leptin and insulin may contribute. More specifically, while insulin increases SNA similarly in lean males and females, this response is markedly ...

    journal_title:Biology of sex differences

    pub_type: 杂志文章,评审


    authors: Shi Z,Wong J,Brooks VL

    更新日期:2020-03-11 00:00:00

  • Investigating transcriptome-wide sex dimorphism by multi-level analysis of single-cell RNA sequencing data in ten mouse cell types.

    abstract:BACKGROUND:It is a long established fact that sex is an important factor that influences the transcriptional regulatory processes of an organism. However, understanding sex-based differences in gene expression has been limited because existing studies typically sequence and analyze bulk tissue from female or male indiv...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Lu T,Mar JC

    更新日期:2020-11-05 00:00:00

  • Age-period-cohort effects in pre-existing and pregnancy-associated diseases amongst primiparous women.

    abstract:BACKGROUND:The average age at first birth is steadily increasing in developed countries; however, demographic shifts in maternal age at childbearing have not occurred in isolation. While temporal increases in adverse pregnancy outcomes are typically attributed to increases in maternal age, little is known about how mat...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Metcalfe A,Ahmed SB,Nerenberg K

    更新日期:2020-04-19 00:00:00

  • Novel human sex-typing strategies based on the autism candidate gene NLGN4X and its male-specific gametologue NLGN4Y.

    abstract:BACKGROUND:Since the early days of PCR techniques, sex identification, "sex-typing," of genomic DNA samples has been a fundamental part of human forensic analysis but also in animal genetics aiming at strategic livestock breeding. Most analyses are employing the AMELX/AMELY gene loci on the X and Y chromosomes present ...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Maxeiner S,Sester M,Krasteva-Christ G

    更新日期:2019-12-18 00:00:00

  • Mechanical contributors to sex differences in idiopathic knee osteoarthritis.

    abstract:: The occurrence of knee osteoarthritis (OA) increases with age and is more common in women compared with men, especially after the age of 50 years. Recent work suggests that contact stress in the knee cartilage is a significant predictor of the risk for developing knee OA. Significant gaps in knowledge remain, however...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Nicolella DP,O'Connor MI,Enoka RM,Boyan BD,Hart DA,Resnick E,Berkley KJ,Sluka KA,Kwoh CK,Tosi LL,Coutts RD,Havill LM,Kohrt WM

    更新日期:2012-12-23 00:00:00

  • Sex differences in nicotine-enhanced Pavlovian conditioned approach in rats.

    abstract:BACKGROUND:Nicotine exposure enhances Pavlovian conditioned approach (PCA), or the learned approach to reward-predictive cues. While females show elevated approach to conditioned stimuli compared to males, potentially indicating heightened addiction vulnerability, it is unknown how sex may interact with nicotine to inf...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Stringfield SJ,Madayag AC,Boettiger CA,Robinson DL

    更新日期:2019-07-17 00:00:00

  • Sex-specific influence on cardiac structural remodeling and therapy in cardiovascular disease.

    abstract:BACKGROUND:Cardiovascular diseases (CVDs) culminating into heart failure (HF) are major causes of death in men and women. Prevalence and manifestation, however, differ between sexes, since men mainly present with coronary artery disease (CAD) and myocardial infarction (MI), and post-menopausal women predominantly prese...

    journal_title:Biology of sex differences

    pub_type: 杂志文章,评审


    authors: Kessler EL,Rivaud MR,Vos MA,van Veen TAB

    更新日期:2019-02-04 00:00:00

  • Training emergency physicians in sex- and gender-based medicine: assessing attitudes of program directors and residency graduates.

    abstract:BACKGROUND:Sex and gender influence disease presentation, treatment, healthcare access, and long-term outcomes. It is uncertain to what extent sex- and gender-based medicine (SGBM) content has been integrated into emergency medicine (EM) residency curricula. We aimed to determine if SGBM is being taught in EM residency...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Madsen TE,McGregor AJ

    更新日期:2016-10-14 00:00:00

  • Sex differences in umbilical artery Doppler indices: a longitudinal study.

    abstract:BACKGROUND:Sexual dimorphism in placental size and function has been described. Whether this influences the clinically important umbilical artery (UA) waveform remains controversial, although a few cross-sectional studies have shown sex differences in UA pulsatility index (PI). Therefore, we tested whether fetal sex in...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Widnes C,Flo K,Wilsgaard T,Kiserud T,Acharya G

    更新日期:2018-04-18 00:00:00

  • Turning sex inside-out: Peripheral contributions to sexual differentiation of the central nervous system.

    abstract:: Sexual differentiation of the nervous system occurs via the interplay of genetics, endocrinology and social experience through development. Much of the research into mechanisms of sexual differentiation has been driven by an implicit theoretical framework in which these causal factors act primarily and directly on se...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Swift-Gallant A,Niel L,Monks DA

    更新日期:2012-05-28 00:00:00

  • Reproducibility in animal models of hypertension: a difficult problem.

    abstract::In 2016, the National Institutes of Health mandated that all grant proposals enhance reproducibility through rigor and transparency. In the past few years, physiological outcomes in established animal models of hypertension, in particular in regard to sex differences, have varied from study to study or laboratory to l...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Reckelhoff JF,Alexander BT

    更新日期:2018-12-22 00:00:00

  • Correction to: Female-biased sexual dimorphism of corticotropin-releasing factor neurons in the bed nucleus of the stria terminalis.

    abstract::Following publication of the original article [1], we noticed a number of errors. ...

    journal_title:Biology of sex differences

    pub_type: 杂志文章,已发布勘误


    authors: Uchida K,Otsuka H,Morishita M,Tsukahara S,Sato T,Sakimura K,Itoi K

    更新日期:2019-02-19 00:00:00

  • BMPR2 expression is suppressed by signaling through the estrogen receptor.

    abstract:BACKGROUND:Studies in multiple organ systems have shown cross-talk between signaling through the bone morphogenetic protein receptor type 2 (BMPR2) and estrogen pathways. In humans, pulmonary arterial hypertension (PAH) has a female predominance, and is associated with decreased BMPR2 expression. The goal of this study...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Austin ED,Hamid R,Hemnes AR,Loyd JE,Blackwell T,Yu C,Phillips Iii JA,Gaddipati R,Gladson S,Gu E,West J,Lane KB

    更新日期:2012-02-20 00:00:00

  • Sex-specific cardiac cardiolipin remodelling after doxorubicin treatment.

    abstract:BACKGROUND:Imbalance in lipid metabolism and membrane lipid homeostasis has been observed in numerous diseases including heart failure and cardiotoxicity. Growing evidence links phospholipid alterations especially cardiolipins (CLs) to defects in mitochondrial function and energy metabolism in heart failure. We have sh...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Moulin M,Solgadi A,Veksler V,Garnier A,Ventura-Clapier R,Chaminade P

    更新日期:2015-10-15 00:00:00

  • Sex- and age-related differences in arterial pressure and albuminuria in mice.

    abstract:BACKGROUND:Animal models have become valuable experimental tools for understanding the pathophysiology and therapeutic interventions in cardiovascular disease. Yet to date, few studies document the age- and sex-related differences in arterial pressure, circadian rhythm, and renal function in normotensive mice under bas...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Barsha G,Denton KM,Mirabito Colafella KM

    更新日期:2016-11-14 00:00:00

  • Ischemia and reperfusion injury following cardioplegic arrest is attenuated by age and testosterone deficiency in male but not female mice.

    abstract:BACKGROUND:Cardiovascular disease increases with age in both sexes. Treatment can require cardiac surgery, where the hearts are pre-treated with protective cardioplegic solution before ischemia and reperfusion (I/R). While endogenous estrogen is beneficial in I/R, whether testosterone is involved is uncertain and wheth...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Ghimire A,Bisset ES,Howlett SE

    更新日期:2019-08-23 00:00:00

  • Inflammatory responses to dietary and surgical weight loss in male and female mice.

    abstract:BACKGROUND:Weight loss by surgery or lifestyle changes is strongly recommended for obese individuals to improve metabolic health, but the underlying impairments that persist from a history of obesity remain unclear. Recent investigations demonstrate a persistent inflammatory state with weight loss and bariatric surgery...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Griffin C,Hutch CR,Abrishami S,Stelmak D,Eter L,Li Z,Chang E,Agarwal D,Zamarron B,Varghese M,Subbaiah P,MacDougald OA,Sandoval DA,Singer K

    更新日期:2019-04-03 00:00:00

  • Sex-specific IL-6-associated signaling activation in ozone-induced lung inflammation.

    abstract:BACKGROUND:Acute ozone (O3) exposure has known deleterious effects on the respiratory system and has been linked with respiratory disease and infection. Inflammatory lung disease induced by air pollution has demonstrated greater severity and poorer prognosis in women vs. men. Both severe damage to the bronchial-alveola...

    journal_title:Biology of sex differences

    pub_type: 杂志文章


    authors: Mishra V,DiAngelo SL,Silveyra P

    更新日期:2016-03-05 00:00:00