Sex differences in the genetic basis of morning serum cortisol levels: genome-wide screen identifies two novel loci specific to women.
BACKGROUND
Relatively little is known about the influence of specific genes on cortisol levels, particularly morning cortisol levels.


OBJECTIVE
The objective of this study was to identify quantitative trait loci associated with morning serum cortisol levels.


METHODS
We carried out a genome screen for morning serum cortisol using linkage and association methods tailored for use in large pedigrees. We conducted these analyses both in the whole sample and partitioned by sex.


METHODS
This study was conducted on nine communal Hutterite farms in South Dakota.


METHODS
The Hutterites are a young founder population who practice a communal, farming lifestyle in the western United States and in Canada. Hutterites (n = 504, 53% female) aged 11-89 yr from a single pedigree participated in this study.


METHODS
The main outcome measures were markers significantly linked or associated with variation in morning serum cortisol levels.


RESULTS
One genome-wide significant association was identified in the whole sample on 11p (D11S1981, P = 0.000092). Results of sex-partitioned analyses indicated that this association was restricted to females (females, P = 0.000084; males, P = 0.20). The 146-bp allele at this locus accounted for 7% of the variance in morning cortisol values in females, and females homozygous for the allele had an 89% increase in morning cortisol levels compared with female noncarriers. A second genome-wide significant association in females was identified on 14q (D14S74, P = 0.000091).


CONCLUSIONS
Our results suggest that the genetic determinants of morning cortisol levels may be different for men and women and that loci on 11p and 14q influence morning cortisol levels in women.
Kurina
Lianne M
LM
Department of Health Studies, The University of Chicago, 5841 South Maryland Avenue, MC2007, Chicago, Illinois 60637, USA. lkurina@uchicago.edu
Weiss
Lauren A
LA
Graves
Steven W
SW
Parry
Rodney
R
Williams
Gordon H
GH
Abney
Mark
M
Ober
Carole
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D005260:Female; D018703:Founder Effect; D008040:Genetic Linkage; D005820:Genetic Testing; D015894:Genome, Human; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000235:genetics*; D008297:Male; D012727:Sex Characteristics; D013023:South Dakota
D006854:Hydrocortisone