Why are the causal effects of shared environment so small? Paul Lichtenstein, professor Head of department Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Sweden

Outline The question: Why do we care about shared environment The method: Twin and family methods The empirical results: Very little shared environment for psychiatric phenotypes The meaning: How should we interpret the limited effect of the shared environment? The conclusion: Life is unfair – should we bother?

Familial aggregation WHY?? Genes? Environments? Lichtenstein et al, 2009, Lancet

Nature or Nuture? Environ-ments Genes 1920 1800 1960 1950 1980 1970 Mendel’s inheritance laws rediscovered 1960 1950 DNA discovered 1980 1970 Reaction to Nazism 2000 Development of molecular genetics Left- and environmental concentration on public debate Human genome project After Plomin & Petrill, Intelligence, 1997

The twin method: Correlations

The twin method: Correlations

The twin method: Correlations

The twin method: Correlations

The Twin method: Model fitting MZ = 1.0 DZ = 0.5 1 E A C C A E e a c c a e T1 T2

Sweden best in class Swedish Twin Register The Multi-Generation Register

The Multi-Generation Registry Individuals born in Sweden > 1932 N ~ 9 million Link with biological and adoptive parents N ~ 15 million

Pedigrees from the MGR Full cousins Half cousins Half siblings II:1 II:2 II:3 II:4 II:5 II:6 II:7 III:1 III:2 III:3 III:4 III:5 III:6 III:7 III:8 Full cousins Half cousins Half siblings Full siblings

Extended children-of-twins model (ECOT)

Percentage of Variance Personality: Meta analyses of twin and adoption studies Familial aggregation most often due to genetic factors Environmental effects most often unique for each family member Shared environment (family environment) small (but significant) effect After Loehlin,1992

MaTCH MaTCH http://match.ctglab.nl Contains summary results from 2,748 twin studies 527 studies of the eight PGC disorders

MaTCH – 8 PGC disorders N studies N MZ pairs N DZ pairs   N studies N MZ pairs N DZ pairs Alcohol Dependence 153 94,477 94,196 Anorexia Nervosa 50 18,917 6,458 ADHD 89 86,450 121,139 Autism Spectrum Disorder 26 37,329 68,559 Bipolar Disorder 10 9,251 15,752 Major Depressive Disorder 163 98,314 121,935 Obsessive Compulsive Disorder 24 25,806 31,994 Schizophrenia 12 19,841 29,457

Shared environment - no or small effect Abnormal environment? What phenotype? What is shared environment – really? How much could you expect? Why are people so provoked?

Abnormal environment Severe deprivation during early childhood influence development! Rutter and Romanian adoptees (summarized in JAACAP, 2012) Severe deprivation Quasi-autism Disinhibited attachment Inattention/overactivity Cognitive impairment

Romanian children adopted to British families before and after age 6 months Rutter et al, JAACAP , 2012

What phenotype? Some phenotypes do show clear shared environmental effects Externalizing behavior Criminality Substance abuse Socioeconomic status

Frisell et al, Psychol Med , 2011

Percentage of Variance Convictions for violent criminality Frisell et al, Psychol Med , 2011

Abuse Twin, sibling and adoption studies (Kendler and Sundqvists) Kendler et al, Psychol Med , 2016

Andel av variationen Utbildningsnivå i födelsekohorter Män *Lichtenstein, Pedersen & McClearn, 1992, Acta Sociologica **Fischbein, Lange & Lichtenstein, 1997, Scandinavian Journal of Educational Research

Andel av variationen Utbildningsnivå i födelsekohorter Män Kvinnor? *Lichtenstein, Pedersen & McClearn, 1992, Acta Sociologica **Fischbein, Lange & Lichtenstein, 1997, Scandinavian Journal of Educational Research

Andel av variationen Utbildningsnivå i födelsekohorter Män Kvinnor *Lichtenstein, Pedersen & McClearn, 1992, Acta Sociologica **Fischbein, Lange & Lichtenstein, 1997, Scandinavian Journal of Educational Research

What is (shared) environment?

Percentage of Variance Stressful life events We (our genes) influence our environment The more controllable – the higher heritability Plomin et al, 1990, Psychol Aging

Neighborhood deprivation ”is genetic” Sariaslan et al, Transl Psychiatry , 2016

How about parenting? Parental criticism: Girls 16 year old The child’s genes influence ”parenting” Evocative gene-environment correlation Narusyte et al, 2007, Europ Child & Adol Psychiatry

Shared environment - no or small effect Abnormal environment? What phenotype? What is shared environment – really? How much could you expect? Why are people so provoked?

Shared environment - no or small effect Abnormal environment? What phenotype? What is shared environment – really? How much could you expect? Why are people so provoked?

Conclusion Shared environment have limited effects – especially for severe psychopathology Does not mean that parenting and treatment are meaningless No causal effects of shared environment but causal effects of parenting Life is unfair – would it be better if it was because of the shared environment?