Statistical Approaches for Detecting Transgenerational Genetic Effects in Humans
Transgenerational genetic effects occur when the genes of one generation influence the phenotype of subsequent generations without Mendelian transmission of alleles, possibly through inherited epigenetic effects. The evidence for transgenerational genetic effects in humans comes predominantly from genetic epidemiology studies, which thus presents a number of statistical challenges to their analysis and interpretation. In this chapter, we outline some of the genetic epidemiologic study designs and statistical analysis approaches that have been used to detect these effects and discuss their strengths and weaknesses.
KeywordsAssisted Reproductive Technology Transgenerational Effect Transmission Disequilibrium Test Mendelian Randomization Variance Component Model
We thank the editors for their comments on this chapter. This review was supported in part by NIH grants GM53275 and T32-HG002536.
- Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H, Yu W, Rongione MA, Ekstrum TJ, Harris TB, Launer LJ, Eiriksdottir G, Leppert MF, Sapienza C, Gudnason V, Feinberg AP (2008) Intra-individual change over time in DNA methylation with familial clustering. JAMA 299:2877–2883PubMedCrossRefGoogle Scholar
- Cordell HJ, Barratt BJ, Clayton DG (2004) Case/pseudocontrol analysis in genetic association studies: a unified framework for detection of genotype and haplotype associations, gene-gene and gene-environment interactions, and parent-of-origin effects. Genet Epidemiol 26:167–185PubMedCrossRefGoogle Scholar
- Edwards TL, Gao X (2012) Methods for detecting and correcting for population stratification. Curr Protoc Hum Genet Chap1:1.22.1–14Google Scholar
- Guyton AC (1981) Textbook of medical physiology. W. B. Saunders, Philadelphia, PAGoogle Scholar
- Khoury MJ, Beaty TH, Cohen BH (1993) Fundamentals of genetic epidemiology. Oxford University Press, OxfordGoogle Scholar
- Laird NM, Lange C (2010) The fundamentals of modern statistical genetics. Springer Verlag, New York, NYGoogle Scholar
- Morris NJ, Gray-McGuire C, Stein CM (2009) Mendelian randomization in family data. BMC Proc 15:S7, S45Google Scholar
- Robson EB (1955) Birth weight in cousins. Annals Hum Genet 262–8Google Scholar
- Stratchen T, Reed A (2003) Human molecular genetics, 3rd edn. Garland Science/Taylor & Francis Group, OxfordGoogle Scholar
- Thomas DC (2004) Statistical methods in genetic epidemiology. Oxford University Press, OxfordGoogle Scholar
- Watanabe RM, Valle T, Hauser ER, Ghosh S, Eriksson J, Kohtamèki K, Ehnholm C, Tuomilehto J, Collins FS, Bergman RN, Boehnke M (1999) Familiality of quantitative metabolic traits in Finnish families with non-insulin-dependent diabetes mellitus. Finland-United States Investigation of NIDDM Genetics (FUSION) Study investigators. Hum Hered 49:159–168PubMedCrossRefGoogle Scholar