New paper on GWAS

 2018 Dec;42(8):783-795. doi: 10.1002/gepi.22161. Epub 2018 Sep 24.

The accuracy of LD Score regression as an estimator of confounding and genetic correlations in genome-wide association studies.

Author information

1
Department of Psychology, University of Minnesota Twin Cities, Minneapolis, Minnesota.
2
Mathematical Biology Section, Laboratory of Biological Modeling, NIDDK, National Institutes of Health, Bethesda, Maryland.

Abstract

To infer that a single-nucleotide polymorphism (SNP) either affects a phenotype or is linkage disequilibrium with a causal site, we must have some assurance that any SNP-phenotype correlation is not the result of confounding with environmental variables that also affect the trait. In this study, we study the properties of linkage disequilibrium (LD) Score regression, a recently developed method for using summary statistics from genome-wide association studies to ensure that confounding does not inflate the number of false positives. We do not treat the effects of genetic variation as a random variable and thus are able to obtain results about the unbiasedness of this method. We demonstrate that LD Score regression can produce estimates of confounding at null SNPs that are unbiased or conservative under fairly general conditions. This robustness holds in the case of the parent genotype affecting the offspring phenotype through some environmental mechanism, despite the resulting correlation over SNPs between LD Scores and the degree of confounding. Additionally, we demonstrate that LD Score regression can produce reasonably robust estimates of the genetic correlation, even when its estimates of the genetic covariance and the two univariate heritabilities are substantially biased.

KEYWORDS:

causal inference; genetic correlation; heritability; population stratification; quantitative genetics

PMID:

 

30251275

 

DOI:

 

10.1002/gepi.22161

One thought on “New paper on GWAS

  1. I remember Matt Mcgue’s paper ‘the end of behavioral genetics’ (2008).

    My grandmother (RIP) was born in Bemidji minnesota and my mom in streater ND.

    If you like couch surfing tourism look up the youtube video ‘a tour of streater North dakota’ . Surprisingly its not well known even though its one of the largest cities in the world and set amidst the highest mountains in the world. Makes Beijing and the Himalayas look like a trailer park set in a hilly area created by garbage dumps–there is a garbage dump in prince william county that looks like a mountain. While Beijing has an institute named for C N Yang , streater has a house named after one of the Roosevelts.

    There were lots of relatives all along the MN/ND border some of whom moved to twin cities.

    (Bemidji is near a native american reservation where they had one of those mass school shootings—alot of depressed, alcoholic and dope addicted indians up there–some of my relatives viewed the native americans as worthless, lazy scum–perhaps genetically inferior or defective. Back in 1862 most of the native americans were removed from minnesota (except the ones who were killed–called the Dakota war of 1862 ) and sent to south and north dakota to find a job. They were just lazy homeless people in Minnesota, getting free food like wild rice using their food stamps. I once took my grandma on a ‘swamp walk’ somewhere in MN to see the beavers and tamarack (larch) trees –i thought she would enjoy it–she lost her shoes in the mud. ).
    My other ND relatives moved to places like Colorado, Connecticut, and Utah .

    Some became mormons and got jobs at Hewlett Packard—ND didnt have that fracked oil then so they wanted to find a job which mormons gave them for a price–you have to do missionary work, and maybe donate some of your children to work for the church. Get rid of all that global warming nonsense, and focus on real work ,like selling off the national parks to Exxon.
    In Denver some worked for the water dept in denver, and some became doctor and psychiatrists. (I think originally they wanted to help cure gay people, but they dropped that pretty fast–ND brethren religion is not used in psychiatry.) They lived right near those 2 mass shootings in Denver area—the film ‘bowling for columbine’ by michael moore describes one, and then there was one at a batman movie by a PhD student in neuroscience –and some of my friends and relatives were in that same MD/PhD program.
    The ones who moved to connecticut became musicans and teachers (including one relative now in US Navy band–he preferred playing music to doing to dealing with IEDs –scaredy cat. Whos scared of the big bad wolf, or an IED, or PTSD? I wonder if you can get a PhD degree in PTSD. )
    One of the teachers on that side of my family was teaching at Sandy Hook school in Connecticut when they also had a mass shooting.
    (Social network theorist Granoveter has the ‘6 degrees of freedom’ idea (or ‘lose connections’ or ‘weak ties’. So i am weakly tied to about 5 mass shootings or massacres (minnesota 2, colorado 2, connecticut 1). I could throw in Va Tech where they had one since i am familiar with that area. (I was slightly aquainted with a few people in their economics and mathematical biology depts –one had a PhD from MIT he got under Robert Solow, and got kicked out for teaching his classes under influence of LSD. Most of those people i met in WV since i tend to stay on the other side of the border. Buchanan, Tideman, Cresswell were at VT–i only met Tideman. He gave me a book which i was supposed to return but didn’t get around to it–i hit the road and ran up to the mountains. ).

    https://en.wikipedia.org/wiki/Rat_Park A popular writer Johann Hari (has a book called ‘lost connections’ and another ‘chasing the scream’) discussed that paper by a UBC psychologisdt (his paper was rejected by Science and Nature–i just renewed my AAAS sub today though i can’t afford it nor have time to read it). Thats a different view than GWAS.

    i sat with my mom today (i got her a watch and she gave me some socks) and i showed her this funny youtube video about R Feynman called Tuva or Bust! (she was working on her maps about Tuvalu in indonesia, so i thought she was talking about Tuva which is in mongolelia. )

    Like

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