Genetic Epidemiology Lay Summaries


Discovery of two new gene variants associated with reading and language abilities

Keywords: genetic inheritance, reading, language impairment

What is already known about this subject:

  • Reading and language abilities are at least partly genetically inherited and probably share common genes.
  • Two common childhood disorders of reading and language abilities are reading disability and specific language impairment. Both of these occur for no obvious reason (for example, in children with normal vision, hearing and intelligence, and no lack of educational opportunity).
  • While some genes contributing to reading disability and specific language impairment have been identified, most of the inherited component of variation in reading and language skills is still unexplained.

What this Raine study adds:

  • Genome-wide analysis of DNA data from individuals with a history of reading or language problems and their siblings who participated in the Raine Study and a number of other international studies identified two new gene variants that appear to be associated with reading and language abilities.
  • Further large-scale genetic studies are needed to further understand the genetic inheritance of reading and language abilities, in people with and without reading and language disorders.

Gialluisi, A., et al. (2014). “Genome-wide screening for DNA variants associated with reading and language traits.” Genes, Brain and Behavior 13(7): 686-701. [publink]

Shared genetic basis for blood pressure and depression in adolescent boys

Keywords: blood pressure, depression, children, gene

What is already known about this subject:

  • A relationship exists between blood pressure and depression in children. This relationship is not explained by lifestyle factors such as diet or exercise.
  • Problems with both depression and high blood pressure often emerge during adolescence and then continue throughout adulthood.
  • Both depression and blood pressure are strongly genetically inherited, but it is not yet known if they share common genes.

What this Raine study adds:

  • Blood pressure, measures of anxiety and depression and DNA data collected from Raine participants at 5, 8, 10, 14 years of age suggest a common underlying genetic contribution to the co-occurrence of depressive symptoms and lower blood pressure in adolescents, but only in adolescent boys.
  • Two gene variants were also found to be important in controlling the rate of increase in blood pressure across childhood in boys only.
  • Further study will help improve our understanding of way in which these genes contribute to blood pressure and depression and potentially contribute to new prevention or treatment strategies.

Louise, S., et al. (2014). “Monoamine oxidase a gene polymorphisms common to blood pressure and depression scores in caucasian children.” Journal of Genetics Study 2(2). [publink]

Age of puberty in girls is influenced by which parent their genes come from

Keywords: reproduction, puberty, genetic inheritance, genetic imprinting

What is already known about this subject:

  • There is a wide variation in the age at which puberty occurs in girls. Early puberty is associated with increased risk of diseases such as breast cancer, diabetes and heart disease.
  • Lifestyle factors such as nutrition and physical activity are important in determining the age of onset of puberty, however there is increasing evidence that a complex network of genetic factors is also important.
  • The activity of some genes depends on which parent they were inherited from (called ‘genetic imprinting’). It is not yet clear if the parental origin of genes influences the timing of puberty.

What this Raine study adds:

  • Genetic data from over 180,000 women (including Raine participants) identified 123 gene variants associated with the age of onset of puberty in girls, 29 of which were involved in the production and functioning of hormones.
  • The parent from whom the genes were inherited was also important in determining the timing of puberty.
  • Understanding how genetic imprinting influences puberty and physical maturation may help improve our understanding of how certain diseases are inherited.

Perry, J. R. B., et al. (2014). “Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.” Nature 514(7520): 92-7. [publink]

Identification of genes contributing to the control of blood cortisol levels

Keywords: cortisol, genome-wide association study, genetic inheritance

What is already known about this subject:

  • Cortisol is an important hormone released by the body in response to stress. It has a wide range of effects that include regulation of metabolism, the cardiovascular system, brain function and responses to infection.
  • Cortisol in the blood is usually found bound to a protein called corticosteroid binding globulin. Only unbound (or ‘free’) cortisol can be used by the body, so the amount of binding protein determines how much cortisol is available for the body to use.
  • Variations in cortisol levels have been shown to contribute to an individual’s risk of cardiovascular and psychiatric disease. It is not yet clear how much of this variation in cortisol levels is due to genetic inheritance.

What this Raine study adds:

  • DNA data and cortisol levels from blood samples collected from over 15,000 individuals (including Raine participants) revealed that the main way in which genes influence blood cortisol levels is by controlling the capacity of corticosteroid binding globulin to bind (or hold onto) cortisol.
  • Genes influenced both the reactivity and circulating concentrations of corticosteroid binding globulin, both of which contribute to its ability to bind cortisol.
  • This is the first study to show a genetic basis for variation in cortisol levels between individuals. Further investigation may help in the understanding of how a person’s cortisol levels may contribute to their risk of disease.

Bolton, J. L., et al. (2014). “Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin.” PLoS Genetics 10(7): e1004474. [publink]

Childhood intelligence is determined by many genes

Keywords: genetic inheritance, intelligence, childhood

What is already known about this subject:

  • Intelligence in childhood is strongly linked to many important life outcomes, including educational attainment, income, health and lifespan.
  • It is known that intelligence is strongly genetically inherited, but the genes involved have yet to be identified.

What this Raine study adds:

  • Data from intelligence tests and DNA samples from Raine participants was included in an international sample of nearly 18,000 individuals, and showed that childhood intelligence is inherited and is influenced by a large number of genes, although the specific genes could not be identified.
  • Further genetic studies are required to identify the genes associated with childhood intelligence. Due to the large number of genes involved and the small size of their effects, even larger populations are needed.

Benyamin, B, Bst Pourcain, O S Davis, G Davies, N K Hansell, M-J a Brion, R M Kirkpatrick, et al. 2014. “Childhood Intelligence Is Heritable, Highly Polygenic and Associated with FNBP1L.” Molecular Psychiatry 19 (2) (February): 253-8. doi:10.1038/mp.2012.184. [publink]

Identification of gene variants associated with early language development

Keywords: genetic inheritance, language development, vocabulary, infancy

What is already known about this subject:

  • Learning to speak is an important stage in a child’s development, and most children are able to use two-word sentences by 2 years of age.
  • While it is known that a child’s language abilities are partly determined by his/her genes, the genes involved have not yet been identified.

What this Raine study adds:

  • Genome-wide screening using DNA samples and vocabulary scores from over 10,000 children aged 15-30 months participating in an international study (including Raine) identified a genetic region associated with language development.
  • The number of words spoken in the early stages of language development was associated with genetic variation near the ROBO2 gene.
  • Understanding the genetic factors involved in language development may help to identify children at risk of autism.

St Pourcain, B., Cents, R. A. M., Whitehouse, A. J. O., Haworth, C. M. A., Davis, O. S. P., O’Reilly, P. F., … Davey Smith, G. (2014). Common variation near ROBO2 is associated with expressive vocabulary in infancy. Nature Communications, 5, 4831. doi:10.1038/ncomms5831. [publink]

Anxiety and depression in preschoolers is influenced by a large number of genes

Keywords: genetic inheritance, emotional problems, psychology, preschool children

What is already known about this subject:

  • Anxiety and depression can affect very young children, and emotional problems in pre-schoolers will often continue into childhood.
  • A person’s genes strongly affect their risk of anxiety and depression.
  • Many studies have looked for genes related to anxiety and depression in adults, but very few have looked in children, even though childhood emotional problems are a risk for other childhood problems and also a range of disorders in adulthood.

What this Raine study adds:

  • DNA data and behavioural assessments from children participating in the Raine study and 2 international cohort studies demonstrated that anxiety and depression in preschool children is influenced by a large number of genes, each with a small effect.
  • Anxiety and depression in 3-year olds is genetically similar to anxiety and depression in adults, and genes contributing to preschool anxiety and depression also increase the risk of later psychiatric disorders.

Benke, Kelly S, Michel G Nivard, Fleur P Velders, Raymond K Walters, Irene Pappa, Paul a Scheet, Xiangjun Xiao, et al. 2014. “A Genome-Wide Association Meta-Analysis of Preschool Internalizing Problems.” Journal of the American Academy of Child and Adolescent Psychiatry 53 (6) (June): 667-676.e7. doi:10.1016/j.jaac.2013.12.028. [publink]

Identification of a gene involved in the onset of puberty in boys

Keywords: genetic inheritance, puberty, sexual maturation

What is already known about this subject:

  • Puberty is an important, complex stage of life, during which a series of developmental events occur, including breast and genital development, the start of menstruation and the pubertal growth spurt.
  • Genetic studies examining the timing of puberty generally focus on girls, as it is easy to measure the age at which a girl has her first menstrual period.
  • Little is known about the genes regulating male puberty, and it is possible that genes known to be involved in the start of menstruation in girls are also important in the initiation of puberty in boys.

What this Raine study adds:

  • DNA data and assessments of pubertal development in children participating in a group of international cohorts (including Raine; 6147 girls and 3769 boys) identified the first gene for male puberty. This gene is related to the timing of sexual development and to the pubertal growth spurt.
  • Genes involved in the onset of menstruation in girls and in pre-pubertal weight gain were found to be important in the timing of puberty in both boys and girls.
  • Genes play an important and complex role in controlling the onset of puberty, and there is overlap in the genetic signals between the sexes.

Cousminer, D. L., Stergiakouli, E., Berry, D. J., Ang, W., Groen-Blokhuis, M. M., Körner, A., … Widén, E. (2014). Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty. Human Molecular Genetics, 23(16), 4452-64. doi:10.1093/hmg/ddu150. [publink]

Genetic regulation of stress hormones in adolescents

Keywords: stress hormones, birth weight, genetic inheritance, adolescent

What is already known about this subject:

  • Our bodies release hormones in response to stress. Inappropriate stress responses can have negative effects on the body, and have been linked to chronic diseases including obesity, high blood pressure, depression and heart disease.
  • A child’s environment, both before and after birth, can change the way their body responds to stress. A low birth weight indicates that a child was exposed to a less-than-ideal environment before birth.
  • The genetics of stress responses are not well understood, in particular, it is not known how genetic variation affects stress responses in adolescents, and it is not known if there is a genetic link between markers of stress at birth and stress responsiveness later in life.

What this Raine study adds:

  • Analysis of DNA data and stress hormone levels at 17 years of age in Raine participants identified a gene related to stress hormone levels.
  • No evidence was found for genetic control of the relationship between birth weight and stress hormone levels in adolescence.
  • Identifying children who have abnormal stress responses may offer the chance of interventions designed to reduce their risk of chronic disease later in life.

Anderson, L. N., Briollais, L., Atkinson, H. C., Marsh, J. A., Xu, J., Connor, K. L., … Lye, S. J. (2014). Investigation of genetic variants, birthweight and hypothalamic-pituitary-adrenal axis function suggests a genetic variant in the SERPINA6 gene is associated with corticosteroid binding globulin in the Western Australia pregnancy cohort (Raine) study. PloS One, 9(4), e92957. doi:10.1371/journal.pone.0092957. [publink]

Identification of an otitis media susceptibility gene

Keywords: otitis media, genetic inheritance, preschool children

What is already known about this subject:

  • Middle ear infection (otitis media) is common in children. Some children will have multiple cases of otitis media or have chronic otitis media that lasts for many months.
  • Recurrent otitis media can cause perforation of the eardrum and hearing loss, which can then lead to problems with language development.
  • Around half of a child’s susceptibility to recurrent or chronic otitis media is genetic, but the genes involved have not yet been identified.

What this Raine study adds:

  • DNA data from children with recurrent or chronic otitis media from the Raine cohort and the Western Australian Family Study of Otitis Media confirmed that genes within a region of chromosome 10 contribute to otitis media susceptibility.
  • A gene within this chromosomal region was identified as a potential otitis media susceptibility gene.
  • Further research may help to identify children at genetic risk of recurrent or chronic otitis media.

Rye, Marie S, Elizabeth S H Scaman, Ruth B Thornton, Shyan Vijayasekaran, Harvey L Coates, Richard W Francis, Craig E Pennell, Jenefer M Blackwell, and Sarra E Jamieson. 2014. “Genetic and Functional Evidence for a Locus Controlling Otitis Media at Chromosome 10q26.3.” BMC Medical Genetics 15 (1) (January): 18. doi:10.1186/1471-2350-15-18. [publink]

Genes for otitis media remain unknown

Keywords: genetic inheritance, otitis media, risk factors

What is already known about this subject:

  • Otitis media (inflammation of the middle ear) is common in childhood and may occur repeatedly in some children.
  • Children who have repeated or chronic otitis media often receive multiple antibiotic treatments and may have grommets inserted.
  • Genetics play a large part in a child’s risk of otitis media, and it tends to run in families. Despite this, little is known about the genes that cause otitis media.

What this Raine study adds:

  • DNA data and data from ear examinations in Raine participants and children and their families participating in a study run by the University of Minnesota showed no association between the gene variants examined and otitis media.
  • Further studies are needed to identify genes that increase the risk for otitis media.

Allen, E. K., Manichaikul, A., Chen, W.-M., Rich, S. S., Daly, K. A., & Sale, M. M. (2014). Evaluation of replication of variants associated with genetic risk of otitis media. PloS One, 9(8), e104212. doi:10.1371/journal.pone.0104212. [publink]


Genes associated with adult obesity are also involved in childhood growth

Keywords: adolescent, body mass index, child, genetics, infant, obesity, risk factors

What is already known about this subject:

  • Obesity is a major global public health problem. It is associated with poor mental and physical health, and many children who are obese are more likely to be obese as adults.
  • An individual’s susceptibility to obesity is the result of a combination of genetic, environmental and behavioural factors. Obesity develops over time, and genes related to adult obesity may begin to exert their effects during childhood or even infancy.
  • Studying how genes associated with obesity in adulthood relate to changes in growth patterns across childhood may help improve our understanding of how obesity develops. However, accurate statistical models of childhood growth are required in order to get the correct information from genetic studies.

What this Raine study adds:

  • Different statistical models were compared to assess how well they estimated the body mass index data (calculated from height and weight measurements) for each individual at all of the follow-ups.
  • 17 genetic variants known to be associated with obesity risk in children and adults were measured from the DNA samples of the Raine participants. These genetic variants were associated with rate of growth over childhood and adolescence.
  • Differences in the rate of growth for each of the genetic variants were observed between males and females.
  • This study provides evidence of genetic effects that may identify individuals early in life that are more likely to rapidly increase their body mass index through childhood and be at increased risk of obesity in later life.

Warrington, Nicole M, Yan Yan Wu, Craig E Pennell, Julie a Marsh, Lawrence J Beilin, Lyle J Palmer, Stephen J Lye, and Laurent Briollais. 2013. “Modelling BMI Trajectories in Children for Genetic Association Studies.” PloS One 8 (1) (January): e53897. doi:10.1371/journal.pone.0053897. [publink]

Obesity genes are also important in triggering puberty in girls

Keywords: adiposity, genetic association studies, body mass index, menarche, obesity, women’s health

What is already known about this subject:

  • Obesity is a global health concern, and is associated with poor health outcomes.
  • Girls who are obese are more likely to start menstruating at an early age; they are also likely to be shorter and overweight or obese as adults.
  • Recent studies suggest that genes involved in obesity may also be involved in the timing of puberty, but these relationships need to be confirmed in large population-based studies.

What this Raine study adds:

  • Investigation of the associations between 95 obesity-related genetic variants and pubertal timing in over 90,000 girls of European descent (including Raine participants) revealed a genetic relationship between genes controlling body mass index and the timing of puberty.
  • None of the genetic variants associated with central (abdominal) obesity were related to pubertal timing.
  • The relationship between childhood and adolescent obesity, puberty and adult obesity is complex, and understanding the underlying genetics will help us understand their influence on adult health and disease.

Fernández-Rhodes, L., Demerath, E. W., Cousminer, D. L., Tao, R., Dreyfus, J. G., Esko, T., … Franceschini, N. (2013). Association of adiposity genetic variants with menarche timing in 92,105 women of European descent. American Journal of Epidemiology, 178(3), 451-60. doi:10.1093/aje/kws473. [publink]

Childhood obesity genes also influence growth during puberty

Keywords: puberty, height, growth spurt, obesity, genetics, adolescence

What is already known about this subject:

  • Height growth is a complex process in which genetic inheritance plays an important part.
  • A distinct growth spurt occurs during adolescence that can contribute up to 20% of an individual’s final height.
  •  Specific growth patterns during childhood are associated with both the timing of puberty and health risks in adulthood. Obesity during childhood is linked to earlier puberty, and in turn, earlier puberty is associated with reduced adult height and an increased risk of obesity during adulthood.
  • While it is estimated that genetic inheritance contributes between 60 and 90% of the variation in pubertal growth between individuals, little else is known about the genes themselves and how they influence adult stature.

What this Raine study adds:

  • Genome-wide analysis in over 18,000 individuals (including data from Raine participants: height and weight at 1, 2, 3, 5, 8, 10, 14 and 17, and DNA at 14 and 17 years of age) confirmed that there is a complex genetic relationship between height growth, the timing of puberty and obesity.
  • Ten gene variants were found to be associated with pubertal height growth and half of these were also associated with the timing of puberty, although not all of these genes were related to adult stature.
  • All of the genes identified that were related to childhood obesity were also related to decreased overall pubertal growth.
  • Understanding the effects of specific genes across multiple growth periods may help us to understand how growth patterns in childhood and adolescence affect adult health.

Cousminer, Diana L, Diane J Berry, Nicholas J Timpson, Wei Ang, Elisabeth Thiering, Enda M Byrne, H Rob Taal, et al. 2013. “Genome-Wide Association and Longitudinal Analyses Reveal Genetic Loci Linking Pubertal Height Growth, Pubertal Timing and Childhood Adiposity.” Human Molecular Genetics 22 (13) (July 1): 2735-47. doi:10.1093/hmg/ddt104. [publink]

Genes common to fetal growth and adult height and metabolism

Keywords: birth weight, genetics, blood pressure, height, fetal development, diabetes

What is already known about this subject:

  • Growth and development are regulated by many different genes; some genes act at specific times, while others regulate growth across different developmental stages. Research suggests that there are links between fetal growth and postnatal growth and metabolism.
  • Previous genetic studies have identified genes that are associated with both birth weight and adult diseases, such as type 2 diabetes, hypertension and obesity. Further study is needed to see if there are other genes linking birth weight and adult traits, and if there are, how they work.

What this Raine study adds:

  • This international study of almost 70,000 individuals discovered four new genetic variants and confirmed three previously known genetic variants as being associated with birth weight. Over 1,000 of the individuals included in this study were from the Raine Cohort, using birth size information and DNA from Raine participants and their mothers.
  •  As well as being associated with birth size, five of the genetic variants identified were also associated with adult traits, including type 2 diabetes, blood pressure and height.
  • The remaining two genetic variants were not associated with any traits other than birth weight. These genetic variants were found to be important only during very early life, and may be associated with
    non-skeletal growth.
  • Genes that control fetal growth are also involved in the control of health and disease, and their effects can be seen into adulthood. These genes that link birth weight to adult outcomes may provide clues to the biological pathways involved in the process of normal growth from childhood to adulthood and also in the transition from health to disease.

Horikoshi, Momoko, Hanieh Yaghootkar, Dennis O Mook-Kanamori, Ulla Sovio, H Rob Taal, Branwen J Hennig, Jonathan P Bradfield, et al. 2013. “New Loci Associated with Birth Weight Identify Genetic Links between Intrauterine Growth and Adult Height and Metabolism.” Nature Genetics 45 (1) (January): 76-82. doi:10.1038/ng.2477. [publink]

Stress responses differ in adolescent boys and girls

Keywords: adolescence, development, stress, sex characteristics, cortisol

What is already known about this subject:

  • The body produces the hormone cortisol in response to stress. Cortisol levels vary between individuals and throughout the course of the day, and are influenced by genetics, developmental factors and environmental exposures.
  • Healthy stress responses are an important part of normal function; however abnormal stress responses can affect physical and psychological health.
  • Maturation of the stress-response system occurs around the time of puberty. Puberty also marks the onset of stress disorders in many individuals.
  • Relationships between stress responses and psychological health problems have generally been studied in adults, who often have other co-existing health issues. Studying stress responses in healthy adolescents may provide more useful information about how the stress-response system matures and functions under normal conditions.

What this Raine study adds:

  • Cortisol levels measured in blood and saliva samples from Raine 17-year-olds were close to reported adult levels, confirming that maturation of the stress-response system occurs during late adolescence.
  • Under non-stressful conditions, girls were exposed to higher levels of cortisol, possibly due to the additional influence of sex hormones. Girls using oral contraceptives had similar cortisol levels to boys.
  • Describing normal cortisol exposure and stress responses in healthy adolescents provides a useful baseline for understanding the relationship between abnormal cortisol exposure and disease vulnerability in adolescents, and also provides potential insight into the relationship between stress responses and health and disease during adulthood.

Reynolds, Rebecca M, Hilary L Hii, Craig E Pennell, Ian W McKeague, E Ron de Kloet, Stephen Lye, Fiona J Stanley, Eugen Mattes, and Jonathan K Foster. 2013. “Analysis of Baseline Hypothalamic-Pituitary-Adrenal Activity in Late Adolescence Reveals Gender Specific Sensitivity of the Stress Axis.” Psychoneuroendocrinology 38 (8) (August): 1271-80. doi:10.1016/j.psyneuen.2012.11.010. [publink]


Common genetic variants do not play a role in defining the male-to-female sex ratio at birth

Keywords: genetic inheritance, gender differences, genome-wide screening

What is already known about this subject:

  • Across the world, the birth rate for males is slightly higher than for females. In people of European descent is equates to an average of 106 males being born for every 100 females.
  • Evidence suggests that the male to female birth ratio is at least partly due to genetic factors, although the particular genes involved have not yet been identified.

What this Raine study adds:

  • Genome-wide screening of DNA samples from over 114,000 individuals (including Raine participants) did not find any detectable genetic contribution to the ratio of males to females at birth.
  • The study was well powered to detect small to modestly sized genetic effects, supporting the conclusion that common genetic variants do not play a role in defining the male-to-female sex ratio at birth.
  • This information will help in the design of genome-wide association studies, especially when selecting control groups for diseases specific to either males or females.

Boraska V, Jeroncic A, Colonna V, …, Zeggini E. Genome-wide meta-analysis of common variant differences between men and women. Hum Mol Genet. 2012 Nov 1;21(21):4805-15. [publink]

Identification of two gene variants related to head size

Keywords: brain size, head size, genetic inheritance, genome-wide association study

What is already known about this subject:

  • The size of a person’s skull (‘intracranial volume’) determines the maximum size of their brain.
  • Brain size starts to decrease after early adulthood. As the brain ages and shrinks it becomes more vulnerable to disease. Having a larger brain may help to protect against age-related degeneration.
  • It is known that both head size and brain size are strongly genetically inherited, but it is not known if they are under the control of the same genes.

What this Raine study adds:

  • Genome-wide screening of DNA data from over 8000 elderly participants and over 10,000 children (including Raine participants) identified two gene variants that were associated with head size (intracranial volume).
  • No gene variants were identified that were related to brain size.
  • Understanding the genetic contribution to head size may help to identify those most at risk of age-related degenerative brain diseases later in life.

Ikram, M. A., et al. (2012). “Common variants at 6q22 and 17q21 are associated with intracranial volume.” Nature Genetics 44(5): 539-544. [publink]

Identification of genes associated with a marker of liver disease and how they change with age

Keywords: adolescent, genetics, heart disease, metabolic disease, genome-wide association study

What is already known about this subject:

  • Gamma-glutamyl transferase (GGT) is an enzyme which works inside cells to protect them from damage caused by the by-products of cellular metabolism.
  • GGT activity is commonly measured in blood samples as a marker of liver function. GGT activity has also been linked to diseases including type 2 diabetes, cardiovascular disease, obesity and cancer.
  • GGT activity is strongly genetically determined; however, to date only a small proportion of the genes involved in GGT activity have been identified. It is not clear how GGT activity influences the risk of diseases and whether the risk changes with age.

What this Raine study adds:

  • 3 new genetic variants were discovered for controlling GGT activity, and two previously described genetic variants were confirmed to be related to GGT activity. The study included DNA and blood samples from Raine participants at 14 and 17 years of age.
  • Substantial overlap was found between genes affecting GGT and those affecting common metabolic and inflammatory diseases.
  • Differences in GGT activity between boys and girls were present from 14 years of age, and GGT activity substantially increased between late adolescence and adulthood. One of the newly discovered genetic variants was found to be differently regulated in adults and adolescents.
  • Further investigation of the genetic control of GGT in health and disease and how it changes with age may improve our understanding of a number of diseases.

Middelberg, Rita P, Beben Benyamin, Marleen H M de Moor, Nicole M Warrington, Scott Gordon, Anjali K Henders, Sarah E Medland, et al. 2012. “Loci Affecting Gamma-Glutamyl Transferase in Adults and Adolescents Show Age × SNP Interaction and Cardiometabolic Disease Associations.” Human Molecular Genetics 21 (2) (January 15): 446-55. doi:10.1093/hmg/ddr478. [publink]

Identification of new genes for otitis media

Keywords: otitis media, genetic inheritance, risk factors, genome-wide association study

What is already known about this subject:

  • Otitis media is a common childhood disease characterised by inflammation of the middle ear, often with a build-up of fluid behind the eardrum.
  • It is estimated that genetic inheritance contributes to between 40 and 70 percent of a child’s risk of chronic (three months or more) or recurrent (3 or more episodes in 6 months) otitis media.
  • While some studies have reported genes involved in susceptibility to otitis media, none have used a genome-wide association study to identify otitis media susceptibility genes.

What this Raine study adds:

  • Genome-wide screening of DNA samples from Raine participants together with childhood otitis media data identified 3 genes as potential contributors to otitis media susceptibility.
  • These associations were not reproduced when tested in a cohort with severe otitis media, possibly due to differences in otitis media severity between the two cohorts or issues with sample size.
  • Further studies are warranted to fully investigate the potential role of these genes in otitis media susceptibility in children.

Rye, Marie S., Nicole M. Warrington, Elizabeth S H Scaman, Shyan Vijayasekaran, Harvey L. Coates, Denise Anderson, Craig E. Pennell, Jenefer M. Blackwell, and Sarra E. Jamieson. 2012. Genome-Wide Association Study to Identify the Genetic Determinants of Otitis Media Susceptibility in Childhood. PLoS ONE 7 (10). doi:10.1371/journal.pone.0048215. [publink]

Identification of gene variants associated with infant head size

Keywords: genetic inheritance, infant head circumference, genome-wide association study

What is already known about this subject:

  • Head circumference in infancy is used as a measure of brain size and development.
  • Head size is largely genetically inherited. Gene mutations causing problems with head size have been identified, but it is not known which genes control normal variation in head size.

What this Raine study adds:

  • Analysis of DNA data from over 19,000 individuals (including Raine participants) identified two gene variants associated with infant head circumference. Both of these genes are also associated with adult height, and may be related to skeletal growth.
  • A third gene variant was found to be marginally associated with head circumference. This gene variant may link early brain growth with neurological disease in later life.

Taal, H Rob, Beate St Pourcain, Elisabeth Thiering, Shikta Das, Dennis O Mook-Kanamori, Nicole M Warrington, Marika Kaakinen, et al. 2012. Common Variants at 12q15 and 12q24 Are Associated with Infant Head Circumference. Nature Genetics 44 (5): 532-538. doi:10.1038/ng.2238. [publink]

A gene related to smoking behaviour is also associated with low birth weight in babies born to mothers who smoked during pregnancy

Keywords: birth weight, genetic predisposition to disease, smoking, pregnancy

What is already known about this subject:

  • Babies born to mothers who smoked during pregnancy often have a low birth weight.
  • A recently identified gene variant has been shown to influence the amount a person smokes. Pregnant women with this gene variant were found to be less able to quit smoking while pregnant.
  • It is not yet clear if this gene variant is also able to influence birth weight in babies born to mothers who smoked during pregnancy.

What this Raine study adds:

  • Analysis of DNA samples from over 26,000 women (including mothers participating in the Raine study) found that mothers who smoked and had the gene variant under investigation had babies with lower birth weight.
  • The gene variant was not associated with lower birth weight in babies born to non-smoking mothers.
  • Health interventions that reduce smoking in pregnant women would help to reduce the prevalence of low birth weight.

Tyrrell, J., Huikari, V., Christie, J. T., Cavadino, A., Bakker, R., Brion, M.-J. A., … Freathy, R. M. (2012). Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight, 21(24), 5344-5358. doi:10.1093/hmg/dds372. [publink]

Fetal growth is influenced by interactions between the fetal environment and an obesity risk gene

Keywords: childhood obesity, fetal growth, genetic inheritance, maternal smoking

What is already known about this subject:

  • The FTOgene has recently been identified as an important cause of obesity in both children and adults.
  • It is thought that the FTO gene may begin to increase obesity risk even before birth, but its effects on fetal growth are unknown.
  • Studies have not yet found an association between the FTO gene and birth weight, but this may be because its relatively small genetic effects are being masked by maternal factors that have large effects on fetal growth (such as smoking, alcohol intake, diabetes and high blood pressure).
  •  It is not yet known if considering the effects of genetics and environment together will reveal a role for the FTO gene on fetal growth.

What this Raine study adds:

  • DNA, obstetric, fetal and postnatal growth data from Raine participants and participants in a Dutch birth cohort demonstrated that the FTO gene has opposite effects on growth before and after birth. Children with the obesity risk variant of the FTO gene had the lowest fetal growth during the third trimester of pregnancy but the highest growth during the first year of life.
  • Maternal smoking significantly affected the growth patterns associated with different FTO gene variants: children born to mothers who smoked during pregnancy showed the opposite growth patterns to children born to non-smoking mothers.
  • The FTO gene was confirmed as being an important determinant of childhood obesity and acts in combination with the fetal environment, particularly in relation to maternal smoking.

Marsh, J. A., Pennell, C. E., Warrington, N. M., Mook-Kanamori, D., Briollais, L., Lye, S. J., … Palmer, L. J. (2012). Fat mass and obesity-associated obesity-risk genotype is associated with lower foetal growth: an effect that is reversed in the offspring of smoking mothers. Journal of Developmental Origins of Health and Disease. doi:10.1017/S2040174411000638. [publink]